Monkeypox is a zoonotic viral infection caused by monkeypox virus which belongs to the Poxviridae family of genus Orthopoxvirus. Usually the virus transmission happens when the individual comes in contact with the infected person through body fluids, animal lesions, respiratory droplets or through virus contaminated materials. Clinical presentation of the monkeypox has shown significant resemblance to that of smallpox and chickenpox, belonging to the same orthopoxvirus genus but were eradicated during 1980s globally. Monkeypox may lead to a range of medical complications including clinical symptoms like fever, rashes, headaches, back pain, myodynia and swollen lymph nodes. As far as the treatment modalities are concerned,the antiviral therapeutic agents developed for the smallpox treatment, were also permitted to be used for the monkeypox treatment. However, there is no proven treatment for human monkeypox. in the current study, we have focused on designing of a best probable ligand against the target MPXVgp158 (Monkeypox virus protein). Since tecovirimat is an FDA approved compound known as an antipoxviral drug, the study aimed to develop a Monkeypox virus protein MPXVgp158 inhibitor which is bioavailable and biocompatible as well through drug designing using computational tools. Molecular docking (MD) analysis displayed tecovirimat with lesser binding energy, higher non-bonded interaction capability, and more stability against MPXVgp158, with efficient binding mode of interactions. Hence, tecovirimat was adjudged to be the potential candidate against MPXVgp158 inhibition.
An overview on Monkeypox, Current Paradigms and Advances in its Vaccination, ...Dr Varruchi Sharma
Monkeypox virus is an orthopoxvirus sharing the common genus with variola and vaccinia virus. Most of the monkeypox (MPX) cases had been reported from the central and west African region (the main endemic areas) prior to 2022 but there was a sudden outbreak in May, 2022 disseminating the infections to thousands of people even in non-endemic countries, posing a global public health emergency. MPX was considered a rae and neglected disease, however the 2022 MPX outbreaks in multiple countries attracted attention of worldwide researchers to pace up for carrying out researches on various aspects of MPXV including attempts to design and develop diagnostics, vaccines, drugs and therapeutics counteract MPX. Apart from being a zoonotic disease, the current outbreaks highlighted rapid human-to-human transmission of MPXV, besides the reverse zoonosis has also been documented with recent first report of human-to-dog transmission, urging a call for the importance of one health approach. Atypical and unusual disease manifestations as well asymptomatic MPXV infections have also been observed during 2022 MPX outbreak. the affected patients typically develop a rash resulting in a mild disease followed by recovery with some supportive care and use of antivirals such as tecovirimat, cidofovir and brincidofovir in severe disease cases. Modified vaccinia Ankara (MVA) vaccine with an excellent safety profile has been recommended to patients with higher risk exposure and immunocompromised individuals. Moreover, another vaccine the replication-competent vaccine (ACAM2000) could be a suitable alternative to MVA’s non-availability to some selective immunocompetent individuals. Current review highlights the salient aspects of management and treatment of monkeypox along with underlying promises in terms of therapeutics and a variety of challenges posed due to current global public health emergency situation to counteract MPX.
This slide tries to explain and introduce you to the mRNA Vaccine Technology, describes mRNA Vaccines, Mechanism , Delivery, some research and case study of pandemic and advantages disadvantages & application see for yourself in detail.
Paxlovid and Molnupiravir What Are The Differences.pdfDoriaFang
On November 4, 2021, the Medicines and Healthcare Products Regulatory Agency (MHRA) granted marketing approval for Molnupiravir (trade name: Lagevrio), an oral COVID-19 drug co-developed by Merck and Ridgeback, for the treatment of patients with mild to moderate COVID-19. This is the first oral antiviral drug approved globally for the treatment of mild to moderate COVID-19 in adults.
COVID-19 (An International Trauma): A Brief Analysis on Research Trends, Impa...AnuragSingh1049
Corona virus disease (COVID-19); have been established as an epidemic of the century. COVID-19, a pandemic is spreading its web throughout the world affecting everyone resulting into mass destruction of populations causing human suffering, creating panic, disturbing everyone economically and stressing all kind of development of entire mankind. COVID-19 is a deadly disease that is supposed to be fatal in 4% of cases. In Severe cases this disease produces enormous respiratory harm like pneumonia, gastrointestinal disorders, weakened immune systems, kidney failure or even death. The pathology of COVID-19 is just similar to SARS and Middle Eastern respiratory syndrome (MERS) corona virus infection. There are no drugs or vaccines for corona viruses yet, including COVID-19. According to WHO Corona virus disease (COVID-19) outbreak situation is persisting with 421,792 confirmed cases and 18,883 confirmed deaths till 23 March 2020. Till now, there are no specific vaccines or treatments for COVID-19. Though, there are multiple of clinical trials, evaluations that may result into potential treatments are ongoing.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
An overview on Monkeypox, Current Paradigms and Advances in its Vaccination, ...Dr Varruchi Sharma
Monkeypox virus is an orthopoxvirus sharing the common genus with variola and vaccinia virus. Most of the monkeypox (MPX) cases had been reported from the central and west African region (the main endemic areas) prior to 2022 but there was a sudden outbreak in May, 2022 disseminating the infections to thousands of people even in non-endemic countries, posing a global public health emergency. MPX was considered a rae and neglected disease, however the 2022 MPX outbreaks in multiple countries attracted attention of worldwide researchers to pace up for carrying out researches on various aspects of MPXV including attempts to design and develop diagnostics, vaccines, drugs and therapeutics counteract MPX. Apart from being a zoonotic disease, the current outbreaks highlighted rapid human-to-human transmission of MPXV, besides the reverse zoonosis has also been documented with recent first report of human-to-dog transmission, urging a call for the importance of one health approach. Atypical and unusual disease manifestations as well asymptomatic MPXV infections have also been observed during 2022 MPX outbreak. the affected patients typically develop a rash resulting in a mild disease followed by recovery with some supportive care and use of antivirals such as tecovirimat, cidofovir and brincidofovir in severe disease cases. Modified vaccinia Ankara (MVA) vaccine with an excellent safety profile has been recommended to patients with higher risk exposure and immunocompromised individuals. Moreover, another vaccine the replication-competent vaccine (ACAM2000) could be a suitable alternative to MVA’s non-availability to some selective immunocompetent individuals. Current review highlights the salient aspects of management and treatment of monkeypox along with underlying promises in terms of therapeutics and a variety of challenges posed due to current global public health emergency situation to counteract MPX.
This slide tries to explain and introduce you to the mRNA Vaccine Technology, describes mRNA Vaccines, Mechanism , Delivery, some research and case study of pandemic and advantages disadvantages & application see for yourself in detail.
Paxlovid and Molnupiravir What Are The Differences.pdfDoriaFang
On November 4, 2021, the Medicines and Healthcare Products Regulatory Agency (MHRA) granted marketing approval for Molnupiravir (trade name: Lagevrio), an oral COVID-19 drug co-developed by Merck and Ridgeback, for the treatment of patients with mild to moderate COVID-19. This is the first oral antiviral drug approved globally for the treatment of mild to moderate COVID-19 in adults.
COVID-19 (An International Trauma): A Brief Analysis on Research Trends, Impa...AnuragSingh1049
Corona virus disease (COVID-19); have been established as an epidemic of the century. COVID-19, a pandemic is spreading its web throughout the world affecting everyone resulting into mass destruction of populations causing human suffering, creating panic, disturbing everyone economically and stressing all kind of development of entire mankind. COVID-19 is a deadly disease that is supposed to be fatal in 4% of cases. In Severe cases this disease produces enormous respiratory harm like pneumonia, gastrointestinal disorders, weakened immune systems, kidney failure or even death. The pathology of COVID-19 is just similar to SARS and Middle Eastern respiratory syndrome (MERS) corona virus infection. There are no drugs or vaccines for corona viruses yet, including COVID-19. According to WHO Corona virus disease (COVID-19) outbreak situation is persisting with 421,792 confirmed cases and 18,883 confirmed deaths till 23 March 2020. Till now, there are no specific vaccines or treatments for COVID-19. Though, there are multiple of clinical trials, evaluations that may result into potential treatments are ongoing.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
Bacteriophages come in different sizes and shapes but most of them.docxrock73
Bacteriophages come in different sizes and shapes but most of them have the same basic features: a head or capsid and a tail. A bacteriophage’s head structure, regardless of its size or shape, is made up of one or more proteins which protectively coats the nucleic acid. Though there are some phages that don’t have a tail, most of them do have one attached to its head structure.
How Bacteriophages Work
n oder to infect a host cell, the bacteriophage attaches itself to the bacteria’s cell wall, specifically on a receptor found on the bacteria’s surface. Once it becomes tightly bound to the cell, the bacterial virus injects its genetic material (its nucleic acid) into the host cell. Depending on the type of phage, one of two cycles will occur – the lytic or the lysogenic cycle. During a lytic cycle, the phage will make use of the host cell’s chemical energy as well as its biosynthetic machinery in order to produce phage nucleic acids (phage DNA and phage mRNA) and phage proteins. Once the production phase is finished, the phage nucleic acids and structural proteins are then assembled. After a while, certain proteins produced within the cell will cause the cell wall to lyse, allowing the assembled phages within to be released and to infect other bacterial cells.
Viral reproduction can also occur through the lysogenic cycle. The main difference between the two types of cycles is that during lysogeny, the host cell is not destroyed or does not undergo lysis. Once the host cell is infected, the phage DNA integrates or combines with the bacterial chromosome, creating the prophage. When the bacterium reproduces, the prophage is replicated along with the host chromosomes. Thus, the daughter cells also contain the prophage which carries the potential of producing phages. The lysogenic cycle can continue indefinitely (daughter cells with prophage present within continuing to replicate) unless exposed to adverse conditions which can trigger the termination of the lysogenic state and cause the expression of the phage DNA and the start of the lytic cycle. These adverse conditions include exposure to UV or mutagenic chemicals and desiccation.
http://phages.org/bacteriophage/
Patients in hospitals, especially those on breathing machines, those with devices such as catheters, and patients with wounds from surgery or from burns are potentially at risk for serious, life-threatening infections.
n hospitals, where the most serious infections occur, Pseudomonas can be spread on the hands of healthcare workers or by equipment that gets contaminated and is not properly cleaned.
https://www.cdc.gov/hai/organisms/pseudomonas.html
P. aeruginosa can develop resistance to antibacterials either through the acquisition of resistance genes on mobile genetic elements (i.e., plasmids) or through mutational processes that alter the expression and/or function of chromosomally encoded mechanisms. Both strategies for developing drug resistance can severely limit the therapeutic ...
Detection of Integrons in Multidrug Resistant Wound Isolatesijtsrd
Integrons are mobile genetic structures that carry genes responsible for resistance to different classes of antibiotics. These genetic platforms are disseminated easily among bacteria through horizontal transfer. This makes it possible for bacteria infecting parts of the body including wounds to harbor integrons resulting to poor therapeutic outcomes. This study was conducted to detect the presence of integrons in multidrug resistance isolates from wounds. Three hundred and sixty chronic wound patients were sampled using sterile cotton tipped swab sticks. The specimens were cultured according to standard microbiological procedures. The isolates were characterized by standard biochemical tests. The genomic DNA of the isolates was extracted by boiling method and was sequenced using the Big Dye kit on 3510 ABI sequencer. Antimicrobial susceptibility test was done using disc diffusion method. Multiplex Polymerase Chain Reaction was carried out on The DNA extracts using Class 1 and Class 11 Integron primers. The result shows that all 360 wound swab specimens yielded single bacteria isolate each. Pseudomonas aeruginosa was the most prevalent isolate 44.2 . The antimicrobial susceptibility test indicates that 42 isolates 11.7 were multidrug resistant MDR . Streptomycin attracted the highest resistance of 88.89 . The least resistance was to Imipenem 35.71 . The gel electrophoresis of the Multiplex PCR product indicates that 90.5 of the MDR isolates possess Class 1 Integron, 33.33 possess Class 11 Integron and 23.8 possess both Integron 1 and Integron 11. In conclusion, this study reports high prevalence of Pseudomonas aeruginosa in chronic wound swabs and 11.7 multidrug resistance among all isolates. The study also reports high prevalence of Class 1 Integron in multidrug resistance isolates. It is therefore recommended that stringent infection control measures be adopted to prevent the spread of bacteria harbouring antibiotic resistance genetic structures. Also rational antibiotic policy is recommended to avoid selection of drug resistance under antibiotic pressure. Ere, Justus Ejike | Enwuru, Chika Paulinus | Wachukwu, C. K "Detection of Integrons in Multidrug Resistant Wound Isolates" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-2 , February 2022, URL: https://www.ijtsrd.com/papers/ijtsrd49409.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/49409/detection-of-integrons-in-multidrug-resistant-wound-isolates/ere-justus-ejike
: The COVID-19 pandemic is spreading across the globe at an alarming rate. Corona Virus is a large
family of positive-sense, single-stranded Ribo Nuclic Acid(RNA) viruses that belong to the Nidovirales order. It
was first started in Wuhan, Hubei Province, China and then subsequently spread to dozens of other countries
becoming a global pandemic. COVID-19 manifests with a wide clinical spectrum ranging from asymptomatic
patients to septic shock and multi organ dysfunction. The most common symptoms of patients include fever (98.
6%), fatigue (69.6%), dry cough, and diarrhea. The WHO recommends collecting samples from both the upper
and lower respiratory tracts. This can be achieved through expectorated sputum, broncho-alveolar lavage or
endotrachial aspirate, These samples are then assessed for viral RNA using polymerase chain reaction(PCR).
Patients with pre-existing co-morbidities have a higher case fatality rate. These co-morbidities include diabetes (7.
3%), respiratory disease(6.5%), cardiovascular disease(10.5%), hypertension(6%) and malignncy(5.6%). Patients
without co-morbidities have a lower case fatality rate(0.9%). Preventive measures must focus on optimizing
infection control protocols, self-isolation, and patient isolation during the provision of clinical care. No confirmed
medication or vaccine has been developed. Current treatment strategies are aimed at symptomatic care and
oxygen therapy. Chloroquine phosphate and lopinavir/ritonavir have been suggested. Other suggested anti-virals
include ribavirin and abidor. Usage of personal protective equipment, washing hands, sanitization, social distance
and general awareness can stop transmission of virus. Prophylactic vaccination is required for the future
prevention of COV-related epidemic or pandemic.
Computational Docking Study of the Phytochemical Constituent, Silybin (Silybu...Dr Varruchi Sharma
SARS-CoV-2 is continually evolving with the emergence of new variants with increased viral pathogenicity. The emergence of heavily mutated Omicron (B.1.1.529) with spike protein mutations are known to mediate its higher transmissibility and immune escape that has brought newer challenges for global public health to contain SARS-CoV-2 infection. One has to come up with a therapeutic strategy against the virus so as to effectively contain the infection and spread. Natural phytochemicals are being considered a significant source of bioactive compounds possessing an antiviral therapeutic potential. Being a promising anticancer and chemo-preventive agent, Silybin holds a significant potential to be used as a therapeutic. In the present study, molecular docking of Silybin with Omicron spike protein (7QNW) was carried out. Molecular docking results showed greater stability of Silybin in the active site of the Omicron spike protein with suitable binding mode of interactions. The study reveals that Silybin has the potential to block the host ACE2 receptor-viral spike protein binding; thereby inhibiting the viral entry to human cells. Therefore, Silybin may be further developed as a medication with the ability to effectively combat SARS-CoV-2 Omicron.
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
The severity and mortality of COVID 19 cases has been associated with the Three category such as vaccination status, severity of disease and outcome. Objective presently study was aimed to assess the severity and mortality among covid 19 patients. Methods Using simple lottery random method 100 samples were selected. From these 100 patients, 50 patients were randomly assigned to case group and 50 patients in control group after informed consents of relative obtained. Patients in the case group who being died after got COVID 19 whereas 50 patients in the control group participated who were survive after got infected from COVID 19 patients. Result It has three categories such as a Vaccination status For the vaccination status we have seen 59 patients were not vaccinated and 41 patients was vaccinated out of 100. b Incidence There were 41 patients were vaccinated whereas 59 patients were not vaccinated. c Severity In the case of mortality we selected 50 patients who were died from the Corona and I got to know that out of 50 patients there were 12 24 patients were vaccinated whereas 38 76 patients were non vaccinated. Although for the 50 control survival group total 29 58 patients were vaccinated and 21 42 patients was not vaccinated all graph start. Conclusion we have find out that those people who got vaccinated were less infected and mortality rate very low. Prof. (Dr) Binod Kumar Singh | Dr. Saroj Kumar | Ms. Anuradha Sharma "To Assess the Severity and Mortality among Covid-19 Patients after Having Vaccinated: A Retrospective Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45065.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/45065/to-assess-the-severity-and-mortality-among-covid19-patients-after-having-vaccinated-a-retrospective-study/prof-dr-binod-kumar-singh
New coronavirus inhibitor exhibits antiviral activity Harm Kiezebrink
Searching for inhibitors of coronaviruses, an international team of scientists led by Edward Trybala, from the University of Gothenburg, Sweden, and Volker Thiel, from the University of Berne, Switzerland, identified a compound called K22.
They initially discovered that K22 had antiviral activity against a relatively harmless coronavirus that causes mild cold-like symptoms in humans.
Follow-up experiments showed that the compound was effective against all other coronaviruses tested, including the SARS and MERS coronaviruses.
The researchers also demonstrated efficient inhibition of virus in cells that line the human airways and are the natural port of entry for respiratory viruses.
Determination of the Presence of Pesticides Insecticide Residual Concentratio...ijtsrd
The study was designed to experimentally investigate the presence of permethrin and cypermethrin insecticide residue concentrations in serum samples of albino rats. 60 Albino rats were used in this research which were equally divided into three groups, with the first containing Rats placed under no mosquito net as control, the second containing Rats placed under commercially insecticide treated Mosquito net, and the third containing rats placed under experimentally formulated treated insecticide Mosquito net. The presence of the insecticide concentration in Blood serum samples of the Rats were determined after carefully extracting the serum by solvent extraction technique, and analyzing the extracts by Gas Chromatographic method. Permethrin insecticide and cypermethrin insecticide were detected in the serum samples of the albino Rats. ANOVA results of F 2,57 =9.1,P=0.000 indicates significant difference in the concentration level of the insecticide in the three groups of the Rats. The Post hoc test indicates that, those Rats housed under experimentally formulated mosquito net, Mean=0.8,SD=0.02 , and those placed under commercially insecticide treated Mosquito net, Mean=0.5,SD=0.001 , experienced higher level of concentration of insecticide as compared to controls, Mean=0.00,SD=0.00 those in Group A . The Mean ± S.D for permethrin and cypermethrin insecticides were significantly different from that of controls. 0.9±0.011mg L of Permethrin was detected in samples of week two and three of the commercially insecticide treated Mosquito net and 0.32.±0.01mg L in week one of the experimentally formulated treated insecticide Mosquito net, respectively as indicated in Table 1, while cypermethrin has a highest value of 0.1±0.082mg L in week two, six, and seven of the commercially insecticide treated Mosquito net as well as 0.9±0.082mg L in the experimentally formulated treated insecticide Mosquito net respectively. The values recorded for both insecticides used in this work are within the WHO recommended permissible limit of 0.05mg kg 2.0mg kg. Muktar Haruna Dunari | Hussaini Abubakar | Haruna Abubakar Danyaya | Balarabe Sarki Sagagi "Determination of the Presence of Pesticides/Insecticide Residual Concentrations in Serum Blood Samples of Albino Rats Exposed to Mosquito Net Treated Insecticide over a Long Period as a Case Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38484.pdf Paper Url: https://www.ijtsrd.com/chemistry/chromatography/38484/determination-of-the-presence-of-pesticidesinsecticide-residual-concentrations-in-serum-blood-samples-of-albino-rats-exposed-to-mosquito-net-treated-insecticide-over-a-long-period-as-a-case-study/muktar-haruna-dunari
Potential therapy derived from banana protein is effective against SARS-CoV-2Creative BioMart
On January 13, 2020, a paper was published online touting the creation of a possible therapy that could be used against all known strains of the flu. A week later, the first laboratory-confirmed case of SARS-CoV-2 sparked the two-and-a-half-year COVID-19 pandemic in the United States. Interestingly, before the virus temporarily halted their work, the international team of researchers for this flu paper also investigated treatments for the coronavirus.
This presentation is about the relevance of vaccine as a public health tool against vaccine preventable diseases and the need to accelerate the development of vaccines against malaria and other diseases of global health importance in developing countries such as Nigeria.
O ptimization of hyrozycloroquine in mangement of covid 19Ahmed Ali
A published article which explains in details why hydroxychloroquine provided conflicting results in Covid-19. This because reflection of its pharmacokinetics, especially ion traping.
This review study was conducted on the information of COVID-19 ethio-pathogenesis, clinical features, diagnosis, complication and
Management, and we have compiled the most recent information on the methods and pharmacological agents used in the diagnosis
and treatment of Coronavirus disease, including pharmacological approaches, fluid therapy, oxygen therapy, Adoptive T cell therapy,
Mesenchymal stromal cell therapy, Nano medicine approaches in COVID-19 and Vaccination approaches.
Plausible State-Specific Plans and Recommendations to Avert COVID-19 Communit...Dr Varruchi Sharma
Current article emphasizes upon the strategy to increase the number of tests at the state-level so that majority of the suspected cases could be traced out, isolated and quarantined in order to contain them from becoming a source of infection and coronavirus disease-2019 (COVID-19) dissemination. The objective of the recommended testing is to contain the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Lessons learnt so far points to the fact that earlier the identification and isolation of infected person, lesser are the chances that it would spread. Considering an example of Maharashtra which has reported cases above 20,000 in the last 7 days with 90,000 tests carried out each day with a test positive report (TPR) of 22%-25%. So, assuming that even if 20% of a particular locality in Maharashtra is infected, then at this rate, we shall be able to isolate only 20,000 each day, while rest of the untraced cases already existing in the locality would pass it on to other people, before being isolated. The only solution to stop this cycle is to outnumber the rate of growth of new cases by increasing the number of tests at a very fast pace. In order to contain the infection, our testing rate has to be much higher than the case growth rate.
Bacteriophages come in different sizes and shapes but most of them.docxrock73
Bacteriophages come in different sizes and shapes but most of them have the same basic features: a head or capsid and a tail. A bacteriophage’s head structure, regardless of its size or shape, is made up of one or more proteins which protectively coats the nucleic acid. Though there are some phages that don’t have a tail, most of them do have one attached to its head structure.
How Bacteriophages Work
n oder to infect a host cell, the bacteriophage attaches itself to the bacteria’s cell wall, specifically on a receptor found on the bacteria’s surface. Once it becomes tightly bound to the cell, the bacterial virus injects its genetic material (its nucleic acid) into the host cell. Depending on the type of phage, one of two cycles will occur – the lytic or the lysogenic cycle. During a lytic cycle, the phage will make use of the host cell’s chemical energy as well as its biosynthetic machinery in order to produce phage nucleic acids (phage DNA and phage mRNA) and phage proteins. Once the production phase is finished, the phage nucleic acids and structural proteins are then assembled. After a while, certain proteins produced within the cell will cause the cell wall to lyse, allowing the assembled phages within to be released and to infect other bacterial cells.
Viral reproduction can also occur through the lysogenic cycle. The main difference between the two types of cycles is that during lysogeny, the host cell is not destroyed or does not undergo lysis. Once the host cell is infected, the phage DNA integrates or combines with the bacterial chromosome, creating the prophage. When the bacterium reproduces, the prophage is replicated along with the host chromosomes. Thus, the daughter cells also contain the prophage which carries the potential of producing phages. The lysogenic cycle can continue indefinitely (daughter cells with prophage present within continuing to replicate) unless exposed to adverse conditions which can trigger the termination of the lysogenic state and cause the expression of the phage DNA and the start of the lytic cycle. These adverse conditions include exposure to UV or mutagenic chemicals and desiccation.
http://phages.org/bacteriophage/
Patients in hospitals, especially those on breathing machines, those with devices such as catheters, and patients with wounds from surgery or from burns are potentially at risk for serious, life-threatening infections.
n hospitals, where the most serious infections occur, Pseudomonas can be spread on the hands of healthcare workers or by equipment that gets contaminated and is not properly cleaned.
https://www.cdc.gov/hai/organisms/pseudomonas.html
P. aeruginosa can develop resistance to antibacterials either through the acquisition of resistance genes on mobile genetic elements (i.e., plasmids) or through mutational processes that alter the expression and/or function of chromosomally encoded mechanisms. Both strategies for developing drug resistance can severely limit the therapeutic ...
Detection of Integrons in Multidrug Resistant Wound Isolatesijtsrd
Integrons are mobile genetic structures that carry genes responsible for resistance to different classes of antibiotics. These genetic platforms are disseminated easily among bacteria through horizontal transfer. This makes it possible for bacteria infecting parts of the body including wounds to harbor integrons resulting to poor therapeutic outcomes. This study was conducted to detect the presence of integrons in multidrug resistance isolates from wounds. Three hundred and sixty chronic wound patients were sampled using sterile cotton tipped swab sticks. The specimens were cultured according to standard microbiological procedures. The isolates were characterized by standard biochemical tests. The genomic DNA of the isolates was extracted by boiling method and was sequenced using the Big Dye kit on 3510 ABI sequencer. Antimicrobial susceptibility test was done using disc diffusion method. Multiplex Polymerase Chain Reaction was carried out on The DNA extracts using Class 1 and Class 11 Integron primers. The result shows that all 360 wound swab specimens yielded single bacteria isolate each. Pseudomonas aeruginosa was the most prevalent isolate 44.2 . The antimicrobial susceptibility test indicates that 42 isolates 11.7 were multidrug resistant MDR . Streptomycin attracted the highest resistance of 88.89 . The least resistance was to Imipenem 35.71 . The gel electrophoresis of the Multiplex PCR product indicates that 90.5 of the MDR isolates possess Class 1 Integron, 33.33 possess Class 11 Integron and 23.8 possess both Integron 1 and Integron 11. In conclusion, this study reports high prevalence of Pseudomonas aeruginosa in chronic wound swabs and 11.7 multidrug resistance among all isolates. The study also reports high prevalence of Class 1 Integron in multidrug resistance isolates. It is therefore recommended that stringent infection control measures be adopted to prevent the spread of bacteria harbouring antibiotic resistance genetic structures. Also rational antibiotic policy is recommended to avoid selection of drug resistance under antibiotic pressure. Ere, Justus Ejike | Enwuru, Chika Paulinus | Wachukwu, C. K "Detection of Integrons in Multidrug Resistant Wound Isolates" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-2 , February 2022, URL: https://www.ijtsrd.com/papers/ijtsrd49409.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/49409/detection-of-integrons-in-multidrug-resistant-wound-isolates/ere-justus-ejike
: The COVID-19 pandemic is spreading across the globe at an alarming rate. Corona Virus is a large
family of positive-sense, single-stranded Ribo Nuclic Acid(RNA) viruses that belong to the Nidovirales order. It
was first started in Wuhan, Hubei Province, China and then subsequently spread to dozens of other countries
becoming a global pandemic. COVID-19 manifests with a wide clinical spectrum ranging from asymptomatic
patients to septic shock and multi organ dysfunction. The most common symptoms of patients include fever (98.
6%), fatigue (69.6%), dry cough, and diarrhea. The WHO recommends collecting samples from both the upper
and lower respiratory tracts. This can be achieved through expectorated sputum, broncho-alveolar lavage or
endotrachial aspirate, These samples are then assessed for viral RNA using polymerase chain reaction(PCR).
Patients with pre-existing co-morbidities have a higher case fatality rate. These co-morbidities include diabetes (7.
3%), respiratory disease(6.5%), cardiovascular disease(10.5%), hypertension(6%) and malignncy(5.6%). Patients
without co-morbidities have a lower case fatality rate(0.9%). Preventive measures must focus on optimizing
infection control protocols, self-isolation, and patient isolation during the provision of clinical care. No confirmed
medication or vaccine has been developed. Current treatment strategies are aimed at symptomatic care and
oxygen therapy. Chloroquine phosphate and lopinavir/ritonavir have been suggested. Other suggested anti-virals
include ribavirin and abidor. Usage of personal protective equipment, washing hands, sanitization, social distance
and general awareness can stop transmission of virus. Prophylactic vaccination is required for the future
prevention of COV-related epidemic or pandemic.
Computational Docking Study of the Phytochemical Constituent, Silybin (Silybu...Dr Varruchi Sharma
SARS-CoV-2 is continually evolving with the emergence of new variants with increased viral pathogenicity. The emergence of heavily mutated Omicron (B.1.1.529) with spike protein mutations are known to mediate its higher transmissibility and immune escape that has brought newer challenges for global public health to contain SARS-CoV-2 infection. One has to come up with a therapeutic strategy against the virus so as to effectively contain the infection and spread. Natural phytochemicals are being considered a significant source of bioactive compounds possessing an antiviral therapeutic potential. Being a promising anticancer and chemo-preventive agent, Silybin holds a significant potential to be used as a therapeutic. In the present study, molecular docking of Silybin with Omicron spike protein (7QNW) was carried out. Molecular docking results showed greater stability of Silybin in the active site of the Omicron spike protein with suitable binding mode of interactions. The study reveals that Silybin has the potential to block the host ACE2 receptor-viral spike protein binding; thereby inhibiting the viral entry to human cells. Therefore, Silybin may be further developed as a medication with the ability to effectively combat SARS-CoV-2 Omicron.
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
The severity and mortality of COVID 19 cases has been associated with the Three category such as vaccination status, severity of disease and outcome. Objective presently study was aimed to assess the severity and mortality among covid 19 patients. Methods Using simple lottery random method 100 samples were selected. From these 100 patients, 50 patients were randomly assigned to case group and 50 patients in control group after informed consents of relative obtained. Patients in the case group who being died after got COVID 19 whereas 50 patients in the control group participated who were survive after got infected from COVID 19 patients. Result It has three categories such as a Vaccination status For the vaccination status we have seen 59 patients were not vaccinated and 41 patients was vaccinated out of 100. b Incidence There were 41 patients were vaccinated whereas 59 patients were not vaccinated. c Severity In the case of mortality we selected 50 patients who were died from the Corona and I got to know that out of 50 patients there were 12 24 patients were vaccinated whereas 38 76 patients were non vaccinated. Although for the 50 control survival group total 29 58 patients were vaccinated and 21 42 patients was not vaccinated all graph start. Conclusion we have find out that those people who got vaccinated were less infected and mortality rate very low. Prof. (Dr) Binod Kumar Singh | Dr. Saroj Kumar | Ms. Anuradha Sharma "To Assess the Severity and Mortality among Covid-19 Patients after Having Vaccinated: A Retrospective Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45065.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/45065/to-assess-the-severity-and-mortality-among-covid19-patients-after-having-vaccinated-a-retrospective-study/prof-dr-binod-kumar-singh
New coronavirus inhibitor exhibits antiviral activity Harm Kiezebrink
Searching for inhibitors of coronaviruses, an international team of scientists led by Edward Trybala, from the University of Gothenburg, Sweden, and Volker Thiel, from the University of Berne, Switzerland, identified a compound called K22.
They initially discovered that K22 had antiviral activity against a relatively harmless coronavirus that causes mild cold-like symptoms in humans.
Follow-up experiments showed that the compound was effective against all other coronaviruses tested, including the SARS and MERS coronaviruses.
The researchers also demonstrated efficient inhibition of virus in cells that line the human airways and are the natural port of entry for respiratory viruses.
Determination of the Presence of Pesticides Insecticide Residual Concentratio...ijtsrd
The study was designed to experimentally investigate the presence of permethrin and cypermethrin insecticide residue concentrations in serum samples of albino rats. 60 Albino rats were used in this research which were equally divided into three groups, with the first containing Rats placed under no mosquito net as control, the second containing Rats placed under commercially insecticide treated Mosquito net, and the third containing rats placed under experimentally formulated treated insecticide Mosquito net. The presence of the insecticide concentration in Blood serum samples of the Rats were determined after carefully extracting the serum by solvent extraction technique, and analyzing the extracts by Gas Chromatographic method. Permethrin insecticide and cypermethrin insecticide were detected in the serum samples of the albino Rats. ANOVA results of F 2,57 =9.1,P=0.000 indicates significant difference in the concentration level of the insecticide in the three groups of the Rats. The Post hoc test indicates that, those Rats housed under experimentally formulated mosquito net, Mean=0.8,SD=0.02 , and those placed under commercially insecticide treated Mosquito net, Mean=0.5,SD=0.001 , experienced higher level of concentration of insecticide as compared to controls, Mean=0.00,SD=0.00 those in Group A . The Mean ± S.D for permethrin and cypermethrin insecticides were significantly different from that of controls. 0.9±0.011mg L of Permethrin was detected in samples of week two and three of the commercially insecticide treated Mosquito net and 0.32.±0.01mg L in week one of the experimentally formulated treated insecticide Mosquito net, respectively as indicated in Table 1, while cypermethrin has a highest value of 0.1±0.082mg L in week two, six, and seven of the commercially insecticide treated Mosquito net as well as 0.9±0.082mg L in the experimentally formulated treated insecticide Mosquito net respectively. The values recorded for both insecticides used in this work are within the WHO recommended permissible limit of 0.05mg kg 2.0mg kg. Muktar Haruna Dunari | Hussaini Abubakar | Haruna Abubakar Danyaya | Balarabe Sarki Sagagi "Determination of the Presence of Pesticides/Insecticide Residual Concentrations in Serum Blood Samples of Albino Rats Exposed to Mosquito Net Treated Insecticide over a Long Period as a Case Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38484.pdf Paper Url: https://www.ijtsrd.com/chemistry/chromatography/38484/determination-of-the-presence-of-pesticidesinsecticide-residual-concentrations-in-serum-blood-samples-of-albino-rats-exposed-to-mosquito-net-treated-insecticide-over-a-long-period-as-a-case-study/muktar-haruna-dunari
Potential therapy derived from banana protein is effective against SARS-CoV-2Creative BioMart
On January 13, 2020, a paper was published online touting the creation of a possible therapy that could be used against all known strains of the flu. A week later, the first laboratory-confirmed case of SARS-CoV-2 sparked the two-and-a-half-year COVID-19 pandemic in the United States. Interestingly, before the virus temporarily halted their work, the international team of researchers for this flu paper also investigated treatments for the coronavirus.
This presentation is about the relevance of vaccine as a public health tool against vaccine preventable diseases and the need to accelerate the development of vaccines against malaria and other diseases of global health importance in developing countries such as Nigeria.
O ptimization of hyrozycloroquine in mangement of covid 19Ahmed Ali
A published article which explains in details why hydroxychloroquine provided conflicting results in Covid-19. This because reflection of its pharmacokinetics, especially ion traping.
This review study was conducted on the information of COVID-19 ethio-pathogenesis, clinical features, diagnosis, complication and
Management, and we have compiled the most recent information on the methods and pharmacological agents used in the diagnosis
and treatment of Coronavirus disease, including pharmacological approaches, fluid therapy, oxygen therapy, Adoptive T cell therapy,
Mesenchymal stromal cell therapy, Nano medicine approaches in COVID-19 and Vaccination approaches.
Similar to tecovirimat as a Potential Bioavailable inhibitor against MPXVgp158 established through Molecular Dynamic Simulations and Docking Studies (20)
Plausible State-Specific Plans and Recommendations to Avert COVID-19 Communit...Dr Varruchi Sharma
Current article emphasizes upon the strategy to increase the number of tests at the state-level so that majority of the suspected cases could be traced out, isolated and quarantined in order to contain them from becoming a source of infection and coronavirus disease-2019 (COVID-19) dissemination. The objective of the recommended testing is to contain the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Lessons learnt so far points to the fact that earlier the identification and isolation of infected person, lesser are the chances that it would spread. Considering an example of Maharashtra which has reported cases above 20,000 in the last 7 days with 90,000 tests carried out each day with a test positive report (TPR) of 22%-25%. So, assuming that even if 20% of a particular locality in Maharashtra is infected, then at this rate, we shall be able to isolate only 20,000 each day, while rest of the untraced cases already existing in the locality would pass it on to other people, before being isolated. The only solution to stop this cycle is to outnumber the rate of growth of new cases by increasing the number of tests at a very fast pace. In order to contain the infection, our testing rate has to be much higher than the case growth rate.
Microbial biotechnology by the participation of microorganism also along with microbial derivatives results in useful products for human welfare. In this process the conversion of natural substances to the processed food is done. The processed substrates can be of diverse range such as enzymes, organic acids, alcohols, polymers, and many more. In reference to human health secondary metabolites are significantly important, such an economically important has deeply benefitted humans by establishing variety of industrial microbial strains. In this chapter we have tried in explaining the microbial role in diverse fields in food production.
Ab-initio density functional and docking studies of α-Santalol molecule deriv...Dr Varruchi Sharma
α-Santalol (a sesquiterpene), an organic compound found in sandalwood was assessed for its reactive potential by computing bond length, Mullikan atomic charges, electrostatic potential surfaces, vibrational frequencies, polarizability, dipole moment and IR spectra with different basis sets implying Hartree Fock and Density functional theory (DFT) Redistribution of charges on α-Santalol was reported to be over a larger range along with the the Bond length values of C32-O39 reportedly higher than the corresponding values of O39-H40 suggestive of its reactivity mainly attributed to hydroxyl group (-OH) attached to C32.Molecular docking studies of α-Santalol with the Monkeypoxgp158 protein further indicate that the designed best probable ligand compound showed significant binding affinity i.e ΔG-8.4Kcal/mole across the binding cleft, suggestive of the therapeutic potential of α-Santalol against monkeypox. Quantum mechanical study of electronic structure, ground state properties and electrostatic potential surface study further supports the reactive sites present in α-Santalol.
Role of plant secondary metabolites as potential antimalarial drugs Dr Varruchi Sharma
Malaria is a global problem affecting a large population without any demarcation between developed and developing world communities. The already approved compounds for the treatment of the disease hold significant efficacy but the emergence of resistant strains and reduced efficacy of drugs against the disease leave the scope for the identification of noval natural products as potential therapeutic agents. There are seven major classes of antiplasmodium agents which are plant secondary metabolites and can be used as a potential antimalarial drugs. In the present review, the focus is on the antimalarial compounds which have been isolated from plants which could be potentially used as antimalarial drugs.
PI3Kinase/AKT/mTOR Pathway in Breast Cancer; Pathogenesis and Prevention with...Dr Varruchi Sharma
The most recurrent and considered second most frequent cause of cancerrelated death in women is the breast cancer worldwide. In breast cancer cases patients are usually diagnosed in the beginning at the curable stage. However, its treatment remains a great clinical challenge. A number of studies have been carried out for the treatment of breast cancer which includes the targeted therapies and increased survival rates in women. Essential PI3K/mTOR signaling pathway activation is observed in most breast cancers. The cell growth and tumor development in this case involves phosphoinositide 3 kinase (PI3K)/ Akt/mammalian target of rapamycin (mTOR) pathway. It has been observed, through preclinical and clinical trials, that there are a number of other inhibitors of PI3K/Akt/mTOR pathway, which either alone or in combination with other agents can be used for treatment of cancer. Pre-clinical studies have confirmed that P13K, Akt and mTOR inhibitors achieve anticancer effects by targeting different levels of the PI3K/Akt/mTOR pathway. This chapter evaluates the role of mTOR along with some of its inhibitors and the PI3K/Akt/mTOR pathway in the pathogenesis and prevention of breast cancer.
BIOINFORMATICS AND ITS APPLICATIONS IN ENVIRONMENTAL SCIENCE AND HEALTH AND I...Dr Varruchi Sharma
Bioinformatics in integration to computational biology is a novel field which applies computer to biology, with which biologists are able to make detailed use of biological data for its advancement. In bioinformatics, the computers are used for the storage followed by the processing and analyzing, along with retrieval of large amounts of biologic and genomic data. In recent years, the field of Bioinformatics is gaining more interest. Earlier, the methodology adopted by the researchers to generate, collect followed by the analysis of various types of scientific data, which is the most time consuming and quite expensive for the work to be carried out. On the other hand with the help of computational tools & techniques, software & databases, one can process a large amount of biological data in a short span such as computer-aided drug designing (CADD). Environment and its protection in today’s word are the most challenging. The problems associated with its protection, planning can be resolved by the best bases of Information technology.
Current Perspective on Dominant Negative Mutations: Trends, Scope and Relevance Dr Varruchi Sharma
Despite the advancements in tools and technologies implicated in identifying and characterizing novel genes, there are still a significant number of unknown function proteins. Moreover, the practices employed in order to characterize such proteins have proven to be a futile exercise so far because of many limitations associated with such traditional approaches. Dominant-negative mutations have shown great promise in this direction as the introduction of mutation in the target protein may abolish the protein function and inhibit the function of the simultaneously expressed wild-type protein. These dominant mutations have broader applications in biological processes to study various proteins in terms of their functional aspects, etiological factors, and mechanism of action, paving the way to diagnose many dreadful diseases, including cancer. Considering these facts, the current review emphasizes utilizing the full potential of such dominant-negative mutations in deciphering protein functions and their broad-spectrum applications in biology
PROBING INTO THE EDIBLE VACCINES: NEWER PARADIGMS, SCOPE AND RELEVANCEDr Varruchi Sharma
Vaccines are proved to be boon for the prevention of infectious diseases and provide acquired immunity against life threatening infections. The lethality of infectious diseases has decreased due to vaccination as it is one of the safe and effective measure to control various infectious diseases. A protein which acts as the vaccine, present in food and consumed as the internal composition of food is known as the edible vaccine. As the name suggests, the term “Edible vaccines” was first used by Charles Arntzen in 1990 and refers to plants that produce vitamins, proteins or other nourishment that act as a vaccine against a certain disease. These vaccines are capable to stimulate the body’s immune system to recognize the antigen. Edible vaccines have been the newer form of vaccines which have the power to cover the risks associated with conventional vaccines. The main mechanism of action of edible vaccines is to activate the systemic and mucosal immunity responses against a foreign disease-causing organism. Edible vaccines are produced by the incorporation of the selected desired genes into the plants and then modified to produce the encoded proteins, providing immunity for certain diseases. Identification, isolation and characterization of a pathogenic antigen is important for making an edible vaccine. At present edible vaccine are developed for various veterinary and human diseases such as cholera, measles, hepatitis and foot and mouth diseases. Current review highlights the importance of edible vaccines which could prove to be cost effective, efficient and safe and would not require refrigeration, making them more accessible to poor people as compared to traditional vaccines.
An In-Silico Approach for Designing a Potential Antagonistic Molecule Targeti...Dr Varruchi Sharma
One of the largest families of membrane proteins, the G protein-coupled receptors (GPCRs) has been a very important target of drug discovery as they are involved in having a regulatory role in a variety of signaling pathways at the cellular level in response to external stimuli. Modern in-silico and crystallographic approaches have further made it easier to peep into their structures. In this study, β2 adrenergic receptor (β2AR) has been targeted, and a new ligand molecule using the de-novo approach has been proposed. Using 1-Amino-3-(2,3-dihydro-1H-indol-4-yloxy)-propan-2-ol, the best fitting binding fragments were established with a significant dissociation constant value of 5-7 nanomolar. The flexibility of specific active sites was also investigated, and it was observed that residues 114 (V), 117 (V), 203 (S), 286 (W), and 289 (F) played a crucial role in accommodating ligand for the best binding. Upon examination of the bioavailability parameters, the ligand var9 exhibited significant inhibitory characteristics having lower toxicity values and high drug likeliness properties. Findings certainly hold significance in terms of targeting GPCRs in getting insight into structure-based drug designing and drug discovery.
Oral squamous cell carcinoma (OSCC) has been considered to be the most common malignancy of the head and neck region. OSCC develops as a result of certain genetic and epigenetic variations in the squamous epithelium, which in turn leads to a series of consequences leading to the definitive stage of invasive squamous cell carcinoma. Majority of oral malignancy cases have been associated with specific exposure to certain risk factors such as smoking, smokeless tobacco products, heavy consumption of alcohol, poor oral hygiene, human papilloma virus infection along with other lifestyle factors and dietary changes. There are certain genes named as BIRC2 and BIRC3 belonging to the inhibitors of apoptosis protein (IAP) family which become over-expressed and upregulated during the course of OSCC. The proteins made are pronounced as cIAPs which are inhibitors of specific caspases leading to the suppression of apoptosis induced by a variety of triggering factors.
Current review has brought together all such concrete studies along with diagnostic and therapeutic relevance to OSCC at a single platform so as to understand the etiological factors, mechanism and regulation in oral squamous cell carcinoma. Moreover, the recent emergence of microbiome as a diagnostic and therapeutic target has also been discussed in order to find a sustainable and reliable therapeutic solution to OSCC.
Essence of PTEN: a Broad-Spectrum Therapeutic Target in Cancer Dr Varruchi Sharma
The levels of protein tyrosine phosphorylation within a cell is regulated by protein tyrosine kinases and protein tyrosine phosphatases. These protein tyrosine phosphatases (PTP) can act both as positive and negative regulators during cell cycle progression and signal transduction. Phosphatase activity is shown by Phosphatase and Tensin homolog (PTEN) protein encoded by PTEN gene localized on human chromosome 10. Earlier findings established the role of PTEN as a tumor suppressor in Cowden’s disease, where PTEN mutations resulted in disease outcomes. Subsequent studies found the role of PTEN mutations in various human cancers, making it one of the vastly studied tumor suppressor genes. The current review has been planned to get a deeper insight into the potential role of PTEN in a variety of physiological processes involved in normal development like cell growth, migration, and differentiation along with the factors, regulation, and underlying mechanism
Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disor...Dr Varruchi Sharma
It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite diff erences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove benefi cial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.
GENDER-BIAS SUSCEPTIBILITY OF CORONA VIRUS DISEASE : PEEPING INTO THE FACTORS...Dr Varruchi Sharma
Recent pandemic of corona virus disease caused by a novel coronavirus SARS-CoV-2 in humans is the third outbreak by this family of viruses, which is reminiscent of the SARS-COV outbreak happened in the year 2003. General characteristics of the novel coronavirus (SARS-CoV-2) especially in regards to the disease susceptibility amongst males and females have been focused providing a better understanding of the coronavirus disease (COVID-19) in males, females and children. A thorough literature search for articles in major databases such as PubMed and Google Scholar etc. has been carried out. COVID-19 has been known to have varied symptoms ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Ageing, genetics, comorbidities and many other associated factors may play a crucial role in predisposing an individual towards COVID-19 disease as there exists chronic inflammation, thrombosis and immune response impairment due to SARS-CoV-2 providing a therapeutic window. Current study emphasizes upon the role of gender in morbidity and mortality in patients with COVID-19 with men higher at risk to COVID-19 than women in terms of mortality despite having the similar prevalence of the disease. The study has been well supported by the data available from the hot-spots affected states from Indian subcontinent. However, current evidence is not sufficient to conclude on the gender-bias susceptibility but certainly men have an edge over women in terms of susceptibility towards COVID-19.
Cancer Chemoprevention by Flavonoids, Dietary Polyphenols and Terpenoids Dr Varruchi Sharma
The world population is aging, and cancer is always considered to be one of the major causes of death all over the globe. The advent of recent drug-targeted therapies undoubtedly is going to reduce the incidence of cancer over the coming years. However, the frequency of occurrence of such chronic diseases like cancer would continue to increase. Therefore, the search for a safer and cost-effective treatment is urgently needed. Phytochemicals found in plants, foods, vegetables, tea, etc. have emerged as proven therapeutic compounds modulating signaling pathways involved in cancer. We carried out a structured search of bibliographic databases for peer-reviewed research literature using the keywords: cancer chemoprevention, flavonoids, dietary polyphenols, terpenoids, bioactive, microbiota. Quality of the retrieved papers and characteristic outcomes of the articles included in the study was assessed by employing standard tools and deductive qualitative content analysis methodology. The development of personalized supplements comprising particular phytochemicals has been the key, especially dealing with chronic inflammatory disorders like cancer. Better understanding at the molecular level explains the influence of phytochemicals on human health, which has been extensively covered through this review. Moreover, the wide collection of dietary polyphenols that has significant properties in reference to human health has been highlighted. Furthermore, the etiology of end products of such phytochemicals, especially on the modulation of gut microbiota and the host-microbial interactions thereof, need to be properly understood. The present study summarizes the chemoprevention and treatment of cancer using the bioactive components, including flavonoids, dietary polyphenols, and terpenoids. Likewise, the effect of dietary polyphenols on the human gut microbiota has been realized more recently. However, more research is needed in this field, especially focused on the communications, interlinks between the gut microbiota and polyphenols with the precise mechanism of action.
MULTIFACETED POTENTIAL OF EICHHORNIA CRASSIPES (WATER HYACINTH) LADENED WITH ...Dr Varruchi Sharma
Being an aquatic weed which is growing dense and widespread across many lakes and water bodies, it is of paramount importance to utilize Eichhornia crassipes (commonly known as water hyacinth) for the benefit of the mankind, especially for its value added and medical properties, such as bio-fuel, biogas, bioremediation and therapeutics. Many of the bird sanctuaries and water-bodies have been drastically invaded by this aquatic weed which is really affecting ecological niche and bird migrations. Several researchers have successfully demonstrated the use of water hyacinth in the bio-remediation and as a potential source of renewable energy. Different heavy and toxic metals showing biomagnifications and therefore creating health hazards, could be remediated by using water hyacinth. The process of decontaminating agro-industrial waste polluted with heavy metals, organic and inorganic pollutants could possibly be done using water hyacinth. Current review focuses towards the efforts to utilize this weed for different value added and therapeutic properties. Furthermore the article emphasizes upon the need to gain more insight into the mechanism with concrete randomized controlled studies to find out the effects of this weed on human health and a sustainable solution to exploit and manage this invasive otherwise harmful weed into a beneficial entity for the mankind.
Disease can occur due to alterations in many physiological processes. A variety of factorsare known to be involved in the progression of cancer, a chronic diseasethat occurs due to permissible proliferative signaling, avoiding growth suppressors, resisting cell death, allowing replicative immortality, induction of angiogenesis, and inducing invasion and metastasis, along with reprogramming of metabolic pathways involved in energy production and avoiding the host immune response for cell destruction. Treatment of such a multifactorial disease has very less cure rate because of the singular agents tried in the past for targeting. Molecular level studies with deeper insight are urgently neededthat focus on the most promising herbal-derived bioactive substances for which thorough research was carried out in the literature in various data-bases such as PUB-MED, MEDLINE, SCOPUS indexed journals etc. to look for systematic reviews of the protocols or data interpretation, natural drug/immunological properties and validation. As immune system plays avery important role in the proliferation or suppression of cancer and other autoimmune diseases, It is the dire need to study the effect of such natural compound on the immune system so that a possible drug target or epitope can be identified for the treatment of such diseases. In nutshell there are many nonclinical in vitro and in vivo studies on herbal medicines which commonly supports the traditional therapeutic claims. It has been seen from the previos studies in literature that the yield and composition of bioactive compounds derived from plants are dependent upon the production source,culturing conditions and extraction protocols.Therefore appropriate optimization conditions would certainly assist the medical and scientific fraternity to accept herbal products as potential candidates for cancer treatment. In this article we explored the different natural products, their immunological effects concerning cancer with no or negligible side effects. However,one has to look for potential herb–drug or herb-epitope interactions and how immune system responds to such drugs.
Role of plant secondary metabolites as potential antimalarial drugsDr Varruchi Sharma
Malaria is a global problem affecting a large population without any demarcation between developed and developing world communities. The already approved compounds for the treatment of the disease hold significant efficacy but the emergence of resistant strains and reduced efficacy of drugs against the disease leave the scope for the identification of noval natural products as potential therapeutic agents. There are seven major classes of antiplasmodium agents which are plant secondary metabolites and can be used as a potential antimalarial drugs. In the present review, the focus is on the antimalarial compounds which have been isolated from plants which could be potentially used as antimalarial drugs.
Targeting Omicron (B.1.1.529) SARS CoV-2 spike protein with selected phytoche...Dr Varruchi Sharma
Severe acute respiratory syndrome coronavirus -2 (S ARS-CoV-2) emerging variants particularly those of concern contain numerous mutations that influence the behavior and transmissibility of the virus and could adversely affect the efficacies of existing coronavirus disease 2019 (COVID-19) vaccines and immunotherapies. The emerging SARS-CoV-2 variants have resulted in different waves of the pandemic within the ongoing COVID-19 pandemic. On 26 November 2021 World Health Organization designated omicron (B.1.1.529) as the fifth variant of concern which was first reported from South Africa on November 24, 2021, and thereafter rapidly spread across the globe owing to its very high transmission rates along with impeding efficacies of existing vaccines and immunotherapies. Omicron contains more than 50 mutations with many mutations (26-32) in spike protein that might be associated with high transmissibility. Natural compounds particularly phytochemicals have been used since ancient times for the treatment of different diseases, and owing to their potent anti-viral properties have also been explored recently against COVID-19. In the present study, molecular docking of nine phytochemicals (Oleocanthal, Tangeritin, Coumarin, Malvidin, Glycitein, Piceatannol, Pinosylnin, Daidzein, and Naringenin) with omicron spike protein (7QNW (electron microscopy, resolution 2.40 Å) was done. The docking study revealed that selected ligands interact with the receptor with binding energy in the range of -6.2 to-7.0 kcal/mol. Pinosylnin showed the highest binding energy of -7.0 kcal/mol which may be used as potential ligands against omicron spike protein. Based on the docking studies, it was suggested that these phytochemicals are potential molecules to be tested against omicron SARS-CoV-2 and can be used to develop effective antiviral drugs.
PI3KAktmTOR Intracellular Pathway and Breast Cancer Factors, Mechanism and Re...Dr Varruchi Sharma
The most recurrent cause of cancer-related deaths worldwide in women is the breast cancer. The key to diagnosis is early prediction and a curable stage but still treatment remains a great clinical challenge. Origin of the Problem: A number of studies have been carried out for the treatment of breast cancer which includes the targeted therapies and increased survival rates in women. Essential PI3K/mTOR signaling pathway activation has been observed in most breast cancers. The cell growth and tumor development in such cases involves phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) complex intracellular pathway. Hypothesis: Through preclinical and clinical trials, it has been observed that there are a number of other inhibitors of PI3K/Akt/mTOR pathway, which either alone or in combination with cytotoxic agents can be used for endocrine therapies. Conclusions: Structure and regulation/deregulation of mTOR provides a greater insight into the action mechanism. Also through this review, one could easily scan first and second generation inhibitors for PI3K/Akt/mTOR pathway besides targeted therapies for breast cancer and the precise role of mTOR.
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
How to Split Bills in the Odoo 17 POS ModuleCeline George
Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Basic Civil Engineering Notes of Chapter-6, Topic- Ecosystem, Biodiversity Green house effect & Hydrological cycle
Types of Ecosystem
(1) Natural Ecosystem
(2) Artificial Ecosystem
component of ecosystem
Biotic Components
Abiotic Components
Producers
Consumers
Decomposers
Functions of Ecosystem
Types of Biodiversity
Genetic Biodiversity
Species Biodiversity
Ecological Biodiversity
Importance of Biodiversity
Hydrological Cycle
Green House Effect
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
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This presentation provides an introduction to quantitative trait loci (QTL) analysis and marker-assisted selection (MAS) in plant breeding. The presentation begins by explaining the type of quantitative traits. The process of QTL analysis, including the use of molecular genetic markers and statistical methods, is discussed. Practical examples demonstrating the power of MAS are provided, such as its use in improving crop traits in plant breeding programs. Overall, this presentation offers a comprehensive overview of these important genomics-based approaches that are transforming modern agriculture.
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Abstract
Monkeypox is a zoonotic viral infection caused by monkeypox virus which belongs to the Poxviridae
family of genus Orthopoxvirus. Usually the virus transmission happens when the individual comes
in contact with the infected person through body fluids, animal lesions, respiratory droplets or
through virus contaminated materials. Clinical presentation of the monkeypox has shown significant
resemblance to that of smallpox and chickenpox, belonging to the same orthopoxvirus genus but were
eradicated during 1980s globally. Monkeypox may lead to a range of medical complications including
clinical symptoms like fever, rashes, headaches, back pain, myodynia and swollen lymph nodes. As
far as the treatment modalities are concerned,the antiviral therapeutic agents developed for the
smallpox treatment, were also permitted to be used for the monkeypox treatment. However, there is
no proven treatment for human monkeypox. In the current study, we have focused on designing of a
best probable ligand against the target MPXVgp158 (Monkeypox virus protein). Since Tecovirimat is an
FDA approved compound known as an antipoxviral drug, the study aimed to develop a Monkeypox virus
protein MPXVgp158 inhibitor which is bioavailable and biocompatible as well through drug designing
using computational tools. Molecular docking (MD) analysis displayed Tecovirimat with lesser binding
energy, higher non-bonded interaction capability, and more stability against MPXVgp158, with efficient
binding mode of interactions. Hence, Tecovirimat was adjudged to be the potential candidate against
MPXVgp158 inhibition.
Keywords: Monkeypox Virus, Molecular Docking, Molecular Dynamic Simulations, Computer-Aided Drug Designing
Introduction
World Health Organization (WHO)
declared the outbreak of Monkeypox as a global
public health emergency on July 23, 2022 (WHO,
2022).Thediseaseisknowntoaffectvarioustissues
and organs including skin, mucous linings, tonsils,
lymphatic nodes, spleen, eyes, with majority of
symptoms bearing similarity to that of smallpox. 1,2
Monkeypox virus can reach the brain parenchyma
and display neuroinvasive characteristics through
two different routes: olfactory epithelium and
hematogenous penetration.3
The very first report
of isolation of monkeypox virus was reported
from cynomolgus monkeys during the smallpox
like disease outbreaks during the year 1958 in
Copenhagen. The Democratic Republic of the
Congo was the first country to report a monkeypox
case of a nine-months old baby.4
Since then, the
virus has spread throughout Africa, splitting into
clades in Central and West Africa.5,6
Therefore,
the West African clade, bringing the monkeypox
outbreak during the year 2003 in nations like
United Kingdom, Israel, and Singapore, is blamed
for the present outbreak of monkeypox.7,8
More
than 82000 monkeypox cases with laboratory
confirmations were recorded between 1st January
2022 and December 2022 in 110 countries
and territories with 65 deaths.9-12
The virus is
regarded as a possible biological weapon due
to its ability to spread quickly among humans.13
Monkeypox virus is a zoonotic Poxviridae family
Orthopoxvirus belonging to Chordopoxviridae
subfamily and is related to the viruses that cause
cowpox, mousepox, and smallpox.14
Notably,
with almost 200 different genes, Orthopoxvirus
genomes are among the biggest known ones for
animal viruses.15,16
As a result, many researches
have concentrated on the genomic, proteomics,
structural, and morphogenetic organization
of the poxviruses.17
Poxviruses comprising of
double-stranded DNA result in infections that
multiply in the cytoplasm of the host cell.18
The
terminal sections of the monkeypox genome
encode virulence and host range factors, while
the core portion encodes structural proteins and
necessary enzymes. The genome of the smallpox-
causing variola virus shares 96.3% similarities with
that of the monkeypox virus.19
The proteomes of
the monkeypox and vaccinia viruses also have
a lot in common. The vaccinia virus serves as a
model poxvirus in experimental conditions and
is utilised in the smallpox vaccine.17
According
to reports, immunization against smallpox were
also reported to be potentially effective against
monkeypox as well with about 85% of efficacy. 20
Smallpox immunisation programmes have been
discontinued after the disease was proclaimed
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eradicated in 1980. Although it is advised to
use smallpox medications against monkeypox,21
their safety and effectiveness in human beings
has not yet been determined.22
JYNNEOS and
ACAM2000 are the only two vaccines currently
recommendedandapprovedforhumanusebythe
USFDA.9,23
The increase in the hospitalisation rate
among patients with monkeypox indicates that
appropriate therapy is essential that too within
a short period of time.24
Therefore, the present
resurgence of monkeypox shows that medications
and therapies tailored specifically for this disease
are urgently needed. The process of discovery
and testing of new drugs typically take ten years,
since they require numerous steps, including the
identification of early lead, animal studies, and
clinical trials.
Therefore, in the context of an epidemic,
drug repurposing is a tempting choice. One
advantage of the drug repurposing strategy
is the substantial reduction in testing time.
Particularly, medications that were once licenced
for use against different illnesses have undergone
comprehensive toxicity testing and can therefore
be given to the general public without risk.25
Drug repurposing research may be essential
to combating the disease as reported cases of
monkeypox rise globally. In order to forecast
authorised medications that can be utilised
against monkeypox, we offer an in silico molecular
docking study in this direction. We focussed on
the mpxvgp158 protein from the monkeypox virus
that is known to be crucial for the viral replication
cycle. In a recent study, Abduljalil and Elfiky
concluded that Norov-29 and bemnifosbuvir, two
antiviral drugs, can bind to the active site of DNA
dependent RNA polymerase (DdRp) and help in
fighting against human monkeypox virus (HMP)26
demonstrated that eight drugs namely NMCT
and rutaecarpine for A48R, fosdagrocorat and
lixivaptan for I7L, simeprevir for D13L, nilotinib
for A50R, and hypericin and naldemedine for
F13L can be potential targets for the inhibition
of HMP so that fatalities can be decreased.27
D9 decapping enzyme and thymidylate kinase
(TMPK) enzymes of viruses may also make
potent antiviral drugs (Doxorubicin, Cefiderocol,
Tipranavir, and Dolutegravir) targets, according to
earlier research. Drug development pipelines now
include computational tools that allow screening
of libraries of small molecules in order to identify
lead compounds that can be further refined to
create candidate medications for clinical trials.28
Researchers recently showed that Tecovirimat's
efficiency against monkeyviruses was due to its
prospective binding pocket and potential binding
mode with F13, a phospholipase D present in
poxviruses.29
F13 made a significant contribution
to the improvement and infectiousness of
extracellular viruses. The effectiveness of
Tecovirimat has been demonstrated both in vitro
and animal studies.22
Therefore, in order to find
possible inhibitors for the selected drug target, we
docked the Tecovirimat drug against mpxvgp158.
Methodology
The design of a best probable ligand
has been performed following the standard
approach for designing of drug molecules based
on the optimized structure using the Monkeypox
virus protein MPXgp158 as the target. The target
protein was aligned for similar proteins using
BLAST search against the PDB database, revealing
the best template for our target with structural
similarities. Based upon the best similar PDB
structures, ITASSER was used for the homology
modeling.30
PROCHECK and PROSA were used
for the validation of the structures which were
designed. Active site searches were established by
the literature support. To find out the investigation
site for our study, we have selected Tecovirimat as
a ligand molecule which has been reported as the
first antipoxviral drug approved for MPX disease
in US, having an inhibitory effect on MPX.31,32
The same ligand has been explored through
PubChem. In the present study, we performed
docking using AutoDock (parameter version 4.2),
in which preparation of the protein and ligands
PDBQT files along with the creation of grid-box
was accomplished using GUI AutoDock Tools.33
The prepared file in PDBQT format was saved using
AutoGrid, and the grid box was created with Grid
Point Spacing of 0.375 Ao with an even number
of Grid Points. The coordinates of the central grid
point of maps were recorded as 65.756, 65.966,
65.707, respectively. In the docking process,
both ligand/protein are considered rigid (Figure
1). Lamarckian Genetic algorithm was used to
perform Docking studies along with Local Search
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default parameters with ΔG values refering to the
significant binding among the developed ligands.34
The complex generated with the
lowest binding affinity was extracted for MD
simulation process. The top docked complex
of Mpox-tecovirimat, which was showing the
highest binding affinity potential, was further
subjected to MD simulations using the GROMACS
2020.2 package in order to study the structural
deviations in a dynamic environment for a time
scale of 100 nanoseconds. The MD simulations
were subsequently examined based on various
parameters including energy of interaction,
solvation free energy (DGsolv), root mean square
fluctuation (RMSF), solvent accessible surface area
(SASA), angle distribution, Radius of gyration (Rg),
and root mean square deviation (RMSD) values as
a function of time.
Results AND Discussion
The compound Tecovirimat is an antiviral
drug which has been reported to have a promising
activityagainstorthopoxviruses.Inordertocombat
the growing threat of zoonotic diseases, further
research into pharmacopoeia is urgently needed.
Among other poxviruses, monkeypox is now
posing a threat to human survivability. Tecovirimat
is more effective and safer than other licenced
medications like cidofovir and brincidofovir
since cidofovir has dose-limiting nephrotoxicity
and brincidofovir has gastrointestinal and
hepatocellular toxicity. As opposed to the other
medications, Tecovirimat has better overall
tolerability.22,35,36
Tecovirimat, however, is not
approved for use during pregnancy.37
Few recent
studies demonstrated the effectiveness of
Tecovirimat in treating monkeypox patients.
The monkeypox virus was detected in a 37-year-
old immunosuppressed male who received
600 mg of Tecovirimat twice daily for a 2-week
treatment along with doxycycline, ceftriaxone,
and valacyclovir. The results showed no discernible
harmful effects, and the skin flaws vanished right
away.38
The safety of oral Tecovirimat doses during
monkeypox infection was recently evaluated by
one study, and it revealed minimal side effects,
such as fatigue, headache, nausea, itching, and
diarrhea.39
Only a few clinical trials on the use
of Tecovirimat to treat monkeypox disease are
available (NCT05534984, NCT02080767). Trials
are still ongoing. In trials, Tecovirimat oral doses
were given to patients based on their body
weight.Confirmedmonkeypoxpatientsweregiven
oral Tecovirimat twice daily for 14 days at the
prescribeddoseof600mginthreedosesof200mg
each. As a result, lesions gradually disappeared
and no deaths were noted. Each participant in
the study completed the full course of Tecovirimat
therapy regimen. This report has limitations
due to the small number of enrolled patients.40
So, additional large-scale trials are required to
determine Tecovirimat antiviral activity, dosage,
and adverse effects. Even while animal studies can
be convincing, human efficacy in later clinical trials
is not always precisely correlated with efficacy
seen in animals. Tecovirimat safety data could
be gathered from people who have monkeypox
rather than only healthy participants. Thus, human
research with monkeypox are both necessary and
feasible.
In our study, we have tried to explore the
same compound for developing the best potential
bioavailable inhibitor against MPXVgp158 protein.
The highest alignment score revealed among
the query and the database segments which
is in agreement with earlier reports as well.41
Computational drug designing approach was used
to develop MPXVgp158 protein inhibitor. With
MPXVgp158sequenceasaquery,sequence,BLAST
search was carried out against protein database.
ITASSER was used further to perform homology
modeling of the subject and the template. This
was followed by the use of PROCHECK and PROSA
for the model evaluation. As a result, the C-Score,
Z-Score,and G-Factorvaluesofall themodelswere
retrieved. Residual Plot score which is reflective of
the quality of the local model was further assessed
by generating a plot of energies as a function of
the residue sequence position using PROSA. The
model score values obtained bear consistency
Table 1. ITASSER generated energy refined models
No. Model C-Score Core Value G-factors Z-Score
1. V1 -1.43 80.0% -0.64 -8.7
2. V2 -2.10 75.8% -0.91 -9.32
3. V3 -3.96 68.1% -0.73 -9.53
4. V4 -4.26 67.1% -0.73 -9.35
5. V5 -5.00 89.8% -0.79 -12.48
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and are in agreement with the earlier studies.42,43
Model V5 was adjudged as the best model having
89.8%corevalue,withagoodnessfactor(G-factor)
value of -0.79 (shown in Table 1)
The energy refined models of the query
protein (MPXVgp158) were generated using
ITASSER, which were ranked based on the size
of the cluster. Significantly higher C Score values
with better quality are further testimony to the
finalized models which are in agreement with
earlier reports.44
Fromliteraturesupportandinthedocked
Table 2. Bioinformatics analysis of the selected ligand molecules
No. Ligand Best ΔG RMSD Inhibition Constant
Nomenclature Conformation (kcal/mol) Vales (millimolar)
1. Lig15 9 -5.01 4.58 428.48
2. Lig28 6 -4.94 4.66 392.42
3. Lig33 8 -4.77 2.92 401.24
4. Lig38 6 -4.27 2.92 348.77
5. Lig51 9 -5.91 4.7 474. 80
Figure 1. Different modes of docking, selective docking mode for Simulation studies
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Figure 2. Interactional Energy
Figure 3.Complex showing Free energy of Solvation
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Figure 4. System RMS Fluctuation
Figure 5. SASA value for the Mpox-Tecovirimat complex
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complex, the following amino acids i.e. THR at 75,
116, 147, VAL 79, ASP 80, GLU 120, and LYS 151
positions, have been revealed as the best binding
pocket of the target protein.
The seed molecule from PubChem
“Tecovirimat” is capable enough of binding as
well as inhibiting the MPOX virus protein. The
selected lead molecule with the target protein
has been docked using AutoDock4.2 (Figure 1).
Ligand 51 displayed best binding affinity with a ΔG
value of -5.91 kcal/mole (Table 2). The study is in
agreement with previous reports as well.45
MD simulation
Although the Mpoxgp158-Tecovirimat
complex fluctuated at the beginning of the
simulation based on the average Coulomb’s
short-range (Coul-SR) values but became stable
after ten nanoseconds with an average value of
-63.58 KJ/mol (Figure 2). The average Lennard-
Jones short-range (LJ-SR) value was reportedly
higher at the beginning but remained static after
10 ns with an average value of -141.93 KJ/mol.46
The solvation-free energy of the complex was
reported to be static with an average value of
-15 DGsolv (Figure 3). The RMSF values of the
Mpoxgp158-Tecovirimat complex were calculated
to understand the local fluctuations taking place
for assessing the flexibility of the atoms. The
RMSF values for the complex remain under 0.5
nm (Figure 4). Theoretically, the solvent-accessible
surface area (SASA) is indicative of the solvent
accessibility of the protein. Our results are quite
consistent with other studies as well.47
Throughout
the simulations, SASA fluctuated around 180
nm2. SASA value for the Mpoxgp158-Tecovirimat
complexremainedlowinthemiddleofsimulations
(Figure 5). Based on the above observations, we
can conclude that the ligand, Tecovirimat interacts
well with the MPXVgp158 protein. Upon analysis
of the plot of the radius of gyration (Rg) which
was spanning over 100 nanoseconds, the data was
indicativeofthecompactnessoftheproteinduring
MD simulations. Throughout simulations, the
radius of gyration for the Mpoxgp158-Tecovirimat
complex remained stable, having a value of 2.25
nm (Figure 6). The ligands' root mean square
deviation (RMSD) was also recorded in order to
observe ligand stability during simulations. The
RMSD value for Tecovirimat remained higher
till eight nanoseconds but afterwards remained
stable, with a value of 0.3 nm, indicating the
Figure 6. Radius of Gyration of the system
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Figure 7. Increasing RMSD value for Tecovirimat
Figure 8. The angle of Tecovirimat in the binding pocket of Mpox protein
stability of Tecovirimat during MD simulations
(Figure 7). The RMSD values observed are quite in
agreement with earlier studies in the literature.48
The angle of Tecovirimat in the binding pocket of
Mpox protein was also recorded and found stable
with an average value of 93.41°, indicating the
stability of Tecovirimat in the binding pocket of
Mpox protein (Figure 8).
Conclusion
In the present study, we have molecularly
docked Tecovirimat with Mpox protein.
Computational-based drug designing method is
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both time and cost-effective to select compounds
as the best probable drugs for further studies.
Tecovirimat has shown the highest binding energy.
Tecovirimat was found to have lesser binding
energy, higher non-bonded interaction capability,
andmorestabilityagainstMpoxprotein,withgood
binding mode of interactions. Hence, Tecovirimat
wasadjudgedtobethepotentialcandidateagainst
MPXVgp158 inhibition. However, there is a need to
furtheranalyzethetargetforfurtherinvestigations
so as to reduce fatalities caused by the Monkeypox
virus.
Acknowledgments
TheauthorswouldliketothankMaharishi
Markandeshwar (Deemed to be University),
Mullana (Ambala) Haryana for providing the
requisite platform to carry out this study.
Conflict of interest
The authors declare that there is no
conflict of interest.
Authors' contribution
Allauthorslistedhavemadeasubstantial,
direct and intellectual contribution to the work,
and approved it for publication.
Funding
None.
Data availability
All datasets generated or analyzed during
this study are included in the manuscript.
Ethics statement
Not applicable.
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