My current research interest includes Drug Discovery to HCV, CHIKV, MRSA, ESBL E coli. and SARS-CoV-2. Primarily using bioinformatics tools.I am a Microbiologist by training with BSc, MSc and PhD (Ectomycorrhizal Fungi) in Microbiology from University of Delhi. I persued Post Doc in Genetic Immunotherapy lab at Division of John Hopkins in Singapore. There I worked on LAMP targeted and non Targeted DNA Vaccine to SARS-CoV and T and B cell epitope mapping of SARS-CoV Spike and Nucleocapsid proteins.I am currently employed at Department of Microbiology, Ram Lal Anand College, University of Delhi as Associate Prof.
Recent advances in the diagnosis of COVID-19: A bird’s eye view , 2021
Introduction: The COVID-19 pandemic is still escalating and has shaped an extraordinary and press... more Introduction: The COVID-19 pandemic is still escalating and has shaped an extraordinary and pressing need for rapid diagnostics with high sensitivity and specificity. Prompt diagnosis is the key to mitigate this situation. As several diagnostic tools for COVID-19 are already available and still others are under development, mandating a comprehensive review of the efficacy of existing tools and evaluate the potential of others. Areas Covered: Currently explored platforms for SARS-CoV-2 diagnostics and surveillance centered on qRT-PCR, RT-PCR, CRISPR, microarray, LAMP, lateral flow immunoassays, proteomics-based approaches, and radiological scans are overviewed and summarized in this review along with their advantages and downsides. A narrative literature review was carried out by accessing the freely available online databases to encapsulate the developments in medical diagnostics. Expert Opinion: An ideal detection method should be sensitive, specific, rapid, cost-effective, and should allow early diagnosis of the infection as near as possible to the point of care that could alter the current situation for the better. Medical diagnostics is a highly dynamic field as no diagnostic method available for SARS-CoV-2 detection offers a perfect solution and requires more attention and continuous R&D to challenge the present-day pandemic situation
The SARS-CoV-2 has affected millions worldwide and has posed an immediate need for effective phar... more The SARS-CoV-2 has affected millions worldwide and has posed an immediate need for effective pharmacological interventions. Ever since the outbreak was declared, the medical fraternity across the world is facing a unique situation of offering assistance and simultaneously generating reliable data with high-quality evidence to extend the scope of finding a treatment. With no proven vaccine or other interventions available hitherto, there is a frenzied urgency of sharing preliminary data from laboratories and trials to shape a global response against the virus. Several clinical trials with investigational and approved repurposed therapeutics have shown promising results. This review aims to compile the information of the reported molecules approved for emergency use and those under clinical trials and still others with good results in the studies conducted so far. Being an RNA virus, SARS-CoV-2 is prone to mutation thus the possibility of gaining resistance to available drugs is high. Consequently, a cocktail therapy based on drug interaction with different stages of its replicative cycle is desirable to reduce the chances of evolving drug-resistance. Since this virus encodes several proteins, including 16 nonstructural and 4 structural proteins; this review also offers an insight into potential drug targets within SARS-CoV-2.
The coronavirus disease (COVID-19) emerged in Wuhan, China in December 2019. Since then it has sp... more The coronavirus disease (COVID-19) emerged in Wuhan, China in December 2019. Since then it has spread to over 180 countries affecting more than a million individual. This contagious virus gets transmitted from an infected individual through droplets and fomites. Although studies have found viral RNA in the feces sample of affected individuals, the oral fecal route of transmission is yet not established. In a different study, it was found that countries which had a long-standing national BCG vaccination policy are less severely affected than those which didn't. India introduced the BCG vaccine in the year 1948. The policy underwent several revisions and Universal Immunization Programme was launched which later became a part of the Child Survival and Safe Motherhood programme in 1992. The age group bracket of 0 to 28 years is hence a better candidate for studying the effect of BCG vaccination on COVID-19 infection in Indian population. Moreover there is immediate need to vaccinate and/or revaccinate everyone associated with healthcare services and also workers involved in manufacturing and supply of essential commodities.
Journal of Biomedical Research & Environmental Sciences, 2020
Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent ye... more Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent years and is getting hard to combat, mandating search for novel therapeutics with a broad antibacterial spectrum and high chemotherapeutic index. The 24 kDa domain of DNA gyrase B that is involved in the ATPase activity has been reported to be a promising target for inhibitors. A PDB structure (1KZN) of the 24kD domain of gyrase B with the co-crystallized ligand clorobiocin was used for the docking studies to explore a library of 2924 FDA approved drugs from www.zinc.docking.org. FlexX docking module from Biosolve IT was used for receptor preparation and in silico docking experiments. Docking studies on the pocket created around the reference ligand clorobiocin revealed the best score with diminazene aceturate and it also demonstrated interactions with the crucial amino acids present within the pocket. Diminazene aceturate has been conventionally been used as an antiparasitic molecule in a...
Journal of Biomedical Research & Environmental Sciences, 2020
The Green House Gas Emission (GHGs) from the carp culture ponds (n = 12) of West Godavari, Krishn... more The Green House Gas Emission (GHGs) from the carp culture ponds (n = 12) of West Godavari, Krishna, and Guntur districts of Andhra Pradesh and from the ponds (n = 4) of Moyna, East Medinipur district of West Bengal, India was assessed through carbon storage and carbon footprint analysis. The average inputs as Carbon Equivalent (CE) were 14407 ± 2651, and 9231 ± 1007 kg/ha in Andhra Pradesh, and West Bengal, respectively. The average carbon storage were 6216 ± 2291, and 5360 ± 1439 kg/ha, in Andhra Pradesh, and Moyna, West Bengal respectively. The emissions of CO2-e and CH4-e were 1.91 ± 0.42 kg CO2-e/kg fish and 0.122 ± 0.027 kg CH4-e/kg fish, respectively in Andhra Pradesh. The emissions of CO2-e and CH4-e were 0.006 to 2.07 (average 0.72) kg CO2-e /kg fish, and 0.0004 to 0.132 (average 0.046) kg CH4-e /kg fish production, respectively in Moyna, West Bengal.
Ectomycorrhizal (EM) fungi can be grown in surface, submerged as well as solid state cultivations... more Ectomycorrhizal (EM) fungi can be grown in surface, submerged as well as solid state cultivations. While growing, EM fungi excrete several enzymes, phytohormones, siderophores, antimicrobial substances as well as organic acids like oxalic acid. These are slow growing fungi with a doubling time of around 50 hours. The EM fungi exhibit physiological as well as ecological diversity within and among species. Variations are seen in biochemical function measured by enzyme production and regulation, production of phytohormones and substances which may be crucial to the symbiotic balance. Many EM fungi are bifactorial with multiple A and B alleles. The attempts to understand EM fungus-plant root interactions have suggested the involvement of symbiosis specific proteins, called ectomycorrhizins. The possibilities of induction of mutations, generation of protoplasts and their regeneration with at least Hebeloma and Laccaria, and transformation of EM fungi have been reported. These features of EM fungi make them suitable for use as experimental organisms.
Chandipura virus (CHPV), alike other pathogens, exploits the cellular infrastructure of their hos... more Chandipura virus (CHPV), alike other pathogens, exploits the cellular infrastructure of their hosts through complex network of interactions for successful infection. CHPV being a recently emerged pediatric encephalitic virus, the mechanisms involved in the establishment of viral persistence are still ill defined. Because the protein interface between CHPV and its host provides one means by which the virus invades and seize control of their human host machinery, the authors in this study have employed computational methods to create a network of putative protein-protein interactions between CHPV and its human host to shed light on the hitherto less-known CHPV biology. On the basis of the 2105 potential interactions predicted among 1650 human proteins and the five proteins of CHPV, the authors decipher the probable mode by which the virus manipulates the biological pathways of its host toward its own end and replicates while evading the immune system. Identification of such conserved set of putative interactions that allow the virus to take control of the host has the potential to deepen our understanding of the virus-specific remodeling processes of the host cell and illuminate new arenas of disease intervention.
... Molecular (Simon er а/., 1993а) and fossil (Remy et al, 1994; Taylor, 1986) evidences togethe... more ... Molecular (Simon er а/., 1993а) and fossil (Remy et al, 1994; Taylor, 1986) evidences together indicate that symbiotic interactions ... including Basidiomycetes, Ascomycetes and Oomycetes (Gardes et al, 1991), for isolate identification of Lacearía, Tuber aestivum (Guillemaud et al ...
Journal of Industrial Microbiology & Biotechnology, 2011
Alkaliphiles are interesting groups of extremophilic organisms that thrive at pH of 9.0 and above... more Alkaliphiles are interesting groups of extremophilic organisms that thrive at pH of 9.0 and above. Many of their products, in particular enzymes, have found widespread applications in industry, primarily in the detergent and laundry industries. While the enzymes have been a runaway success from the industrial point of view, many more products have been reported from alkaliphiles such as antibiotics and carotenoids. Less known are their potential for degradation of xenobiotics. They also play a key role in biogeocycling of important inorganic compounds. This review provides an insight into the huge diversity of alkaliphilic bacteria, the varied products obtained from them, and the need for further investigations on these interesting bacteria.
The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over... more The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over 188 countries affecting millions of individuals. Several reports in favour or against the heterologous protection conferred by the BCG vaccine against COVID-19 came up in the initial days of the pandemic and continue to do so. In this study, we compared the three worst-affected nations: The USA, India, and Brazil, their current pandemic scenario, and their respective national BCG immunization policies. USA recommends BCG vaccine only to a specific group of people and never had a national immunization scheme in place. Meanwhile, India introduced a nationwide scheme as early as 1948 and continues to endorse BCG immunization at birth. Brazil used the oral route to administer the BCG vaccine till 1976, and then shifted to intradermal injection. The correlation coefficient for the total number of cases, cases per million, the total number of deaths, deaths per million and case fatality rate ...
The current COVID-19 pandemic has urged the scientific community internationally to find answers ... more The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.
The alarming multiple drug resistance developed by Escherichia coli towards the routine conventio... more The alarming multiple drug resistance developed by Escherichia coli towards the routine conventional antibiotics owing to their non-judicious usage is fast becoming a tough menace. This necessitates the urgent unleashing of novel and diverse strategies and antibacterial compounds. Since fi nding a new antibiotic from the scratch, followed by endless clinical trials is exceedingly time-consuming, a powerful alternate strategy of CADD coupled with repurposing the available drugs could save precious time and money. DNA gyrases (topoisomerase II) of E.coli are among the promising new drug targets. The interface between the N-terminal domain of gyrA and C-terminal domain of gyrB which is targeted by most of the available inhibitory drugs, is of particular interest. Crucial active site residues within the N-terminal domain of gyrA were delineated through a literature search. FDA approved drugs were docked using FlexX on the receptors created around the co-crystallized reference ligand. Based on the docking scores and interactions with crucial residues, 12 leads were shortlisted, namely ceforanide, tetrahydrofolic acid, azlocillin, cefazolin, adenosine triphosphate, cefi xime, dihydronicotinamide adenine dinucleotide, moxalactam, leucal, cromoglicic acid, cefotetan, and cedax. Surprisingly quinolones, which are approved inhibitors of gyrases were not picked up in the top leads, rather, the most dominant class of molecules that docked successfully was cephalosporin. Our results indicated that these cephalosporins, as well as the other shortlisted leads, could be further optimized and validated through in-vitro experiments for their potential as gyrase A antagonists. Hence the present study holds immense promise in combating MDR of human bacterial pathogens.
Recent advances in the diagnosis of COVID-19: A bird’s eye view , 2021
Introduction: The COVID-19 pandemic is still escalating and has shaped an extraordinary and press... more Introduction: The COVID-19 pandemic is still escalating and has shaped an extraordinary and pressing need for rapid diagnostics with high sensitivity and specificity. Prompt diagnosis is the key to mitigate this situation. As several diagnostic tools for COVID-19 are already available and still others are under development, mandating a comprehensive review of the efficacy of existing tools and evaluate the potential of others. Areas Covered: Currently explored platforms for SARS-CoV-2 diagnostics and surveillance centered on qRT-PCR, RT-PCR, CRISPR, microarray, LAMP, lateral flow immunoassays, proteomics-based approaches, and radiological scans are overviewed and summarized in this review along with their advantages and downsides. A narrative literature review was carried out by accessing the freely available online databases to encapsulate the developments in medical diagnostics. Expert Opinion: An ideal detection method should be sensitive, specific, rapid, cost-effective, and should allow early diagnosis of the infection as near as possible to the point of care that could alter the current situation for the better. Medical diagnostics is a highly dynamic field as no diagnostic method available for SARS-CoV-2 detection offers a perfect solution and requires more attention and continuous R&D to challenge the present-day pandemic situation
The SARS-CoV-2 has affected millions worldwide and has posed an immediate need for effective phar... more The SARS-CoV-2 has affected millions worldwide and has posed an immediate need for effective pharmacological interventions. Ever since the outbreak was declared, the medical fraternity across the world is facing a unique situation of offering assistance and simultaneously generating reliable data with high-quality evidence to extend the scope of finding a treatment. With no proven vaccine or other interventions available hitherto, there is a frenzied urgency of sharing preliminary data from laboratories and trials to shape a global response against the virus. Several clinical trials with investigational and approved repurposed therapeutics have shown promising results. This review aims to compile the information of the reported molecules approved for emergency use and those under clinical trials and still others with good results in the studies conducted so far. Being an RNA virus, SARS-CoV-2 is prone to mutation thus the possibility of gaining resistance to available drugs is high. Consequently, a cocktail therapy based on drug interaction with different stages of its replicative cycle is desirable to reduce the chances of evolving drug-resistance. Since this virus encodes several proteins, including 16 nonstructural and 4 structural proteins; this review also offers an insight into potential drug targets within SARS-CoV-2.
The coronavirus disease (COVID-19) emerged in Wuhan, China in December 2019. Since then it has sp... more The coronavirus disease (COVID-19) emerged in Wuhan, China in December 2019. Since then it has spread to over 180 countries affecting more than a million individual. This contagious virus gets transmitted from an infected individual through droplets and fomites. Although studies have found viral RNA in the feces sample of affected individuals, the oral fecal route of transmission is yet not established. In a different study, it was found that countries which had a long-standing national BCG vaccination policy are less severely affected than those which didn't. India introduced the BCG vaccine in the year 1948. The policy underwent several revisions and Universal Immunization Programme was launched which later became a part of the Child Survival and Safe Motherhood programme in 1992. The age group bracket of 0 to 28 years is hence a better candidate for studying the effect of BCG vaccination on COVID-19 infection in Indian population. Moreover there is immediate need to vaccinate and/or revaccinate everyone associated with healthcare services and also workers involved in manufacturing and supply of essential commodities.
Journal of Biomedical Research & Environmental Sciences, 2020
Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent ye... more Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent years and is getting hard to combat, mandating search for novel therapeutics with a broad antibacterial spectrum and high chemotherapeutic index. The 24 kDa domain of DNA gyrase B that is involved in the ATPase activity has been reported to be a promising target for inhibitors. A PDB structure (1KZN) of the 24kD domain of gyrase B with the co-crystallized ligand clorobiocin was used for the docking studies to explore a library of 2924 FDA approved drugs from www.zinc.docking.org. FlexX docking module from Biosolve IT was used for receptor preparation and in silico docking experiments. Docking studies on the pocket created around the reference ligand clorobiocin revealed the best score with diminazene aceturate and it also demonstrated interactions with the crucial amino acids present within the pocket. Diminazene aceturate has been conventionally been used as an antiparasitic molecule in a...
Journal of Biomedical Research & Environmental Sciences, 2020
The Green House Gas Emission (GHGs) from the carp culture ponds (n = 12) of West Godavari, Krishn... more The Green House Gas Emission (GHGs) from the carp culture ponds (n = 12) of West Godavari, Krishna, and Guntur districts of Andhra Pradesh and from the ponds (n = 4) of Moyna, East Medinipur district of West Bengal, India was assessed through carbon storage and carbon footprint analysis. The average inputs as Carbon Equivalent (CE) were 14407 ± 2651, and 9231 ± 1007 kg/ha in Andhra Pradesh, and West Bengal, respectively. The average carbon storage were 6216 ± 2291, and 5360 ± 1439 kg/ha, in Andhra Pradesh, and Moyna, West Bengal respectively. The emissions of CO2-e and CH4-e were 1.91 ± 0.42 kg CO2-e/kg fish and 0.122 ± 0.027 kg CH4-e/kg fish, respectively in Andhra Pradesh. The emissions of CO2-e and CH4-e were 0.006 to 2.07 (average 0.72) kg CO2-e /kg fish, and 0.0004 to 0.132 (average 0.046) kg CH4-e /kg fish production, respectively in Moyna, West Bengal.
Ectomycorrhizal (EM) fungi can be grown in surface, submerged as well as solid state cultivations... more Ectomycorrhizal (EM) fungi can be grown in surface, submerged as well as solid state cultivations. While growing, EM fungi excrete several enzymes, phytohormones, siderophores, antimicrobial substances as well as organic acids like oxalic acid. These are slow growing fungi with a doubling time of around 50 hours. The EM fungi exhibit physiological as well as ecological diversity within and among species. Variations are seen in biochemical function measured by enzyme production and regulation, production of phytohormones and substances which may be crucial to the symbiotic balance. Many EM fungi are bifactorial with multiple A and B alleles. The attempts to understand EM fungus-plant root interactions have suggested the involvement of symbiosis specific proteins, called ectomycorrhizins. The possibilities of induction of mutations, generation of protoplasts and their regeneration with at least Hebeloma and Laccaria, and transformation of EM fungi have been reported. These features of EM fungi make them suitable for use as experimental organisms.
Chandipura virus (CHPV), alike other pathogens, exploits the cellular infrastructure of their hos... more Chandipura virus (CHPV), alike other pathogens, exploits the cellular infrastructure of their hosts through complex network of interactions for successful infection. CHPV being a recently emerged pediatric encephalitic virus, the mechanisms involved in the establishment of viral persistence are still ill defined. Because the protein interface between CHPV and its host provides one means by which the virus invades and seize control of their human host machinery, the authors in this study have employed computational methods to create a network of putative protein-protein interactions between CHPV and its human host to shed light on the hitherto less-known CHPV biology. On the basis of the 2105 potential interactions predicted among 1650 human proteins and the five proteins of CHPV, the authors decipher the probable mode by which the virus manipulates the biological pathways of its host toward its own end and replicates while evading the immune system. Identification of such conserved set of putative interactions that allow the virus to take control of the host has the potential to deepen our understanding of the virus-specific remodeling processes of the host cell and illuminate new arenas of disease intervention.
... Molecular (Simon er а/., 1993а) and fossil (Remy et al, 1994; Taylor, 1986) evidences togethe... more ... Molecular (Simon er а/., 1993а) and fossil (Remy et al, 1994; Taylor, 1986) evidences together indicate that symbiotic interactions ... including Basidiomycetes, Ascomycetes and Oomycetes (Gardes et al, 1991), for isolate identification of Lacearía, Tuber aestivum (Guillemaud et al ...
Journal of Industrial Microbiology & Biotechnology, 2011
Alkaliphiles are interesting groups of extremophilic organisms that thrive at pH of 9.0 and above... more Alkaliphiles are interesting groups of extremophilic organisms that thrive at pH of 9.0 and above. Many of their products, in particular enzymes, have found widespread applications in industry, primarily in the detergent and laundry industries. While the enzymes have been a runaway success from the industrial point of view, many more products have been reported from alkaliphiles such as antibiotics and carotenoids. Less known are their potential for degradation of xenobiotics. They also play a key role in biogeocycling of important inorganic compounds. This review provides an insight into the huge diversity of alkaliphilic bacteria, the varied products obtained from them, and the need for further investigations on these interesting bacteria.
The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over... more The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over 188 countries affecting millions of individuals. Several reports in favour or against the heterologous protection conferred by the BCG vaccine against COVID-19 came up in the initial days of the pandemic and continue to do so. In this study, we compared the three worst-affected nations: The USA, India, and Brazil, their current pandemic scenario, and their respective national BCG immunization policies. USA recommends BCG vaccine only to a specific group of people and never had a national immunization scheme in place. Meanwhile, India introduced a nationwide scheme as early as 1948 and continues to endorse BCG immunization at birth. Brazil used the oral route to administer the BCG vaccine till 1976, and then shifted to intradermal injection. The correlation coefficient for the total number of cases, cases per million, the total number of deaths, deaths per million and case fatality rate ...
The current COVID-19 pandemic has urged the scientific community internationally to find answers ... more The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.
The alarming multiple drug resistance developed by Escherichia coli towards the routine conventio... more The alarming multiple drug resistance developed by Escherichia coli towards the routine conventional antibiotics owing to their non-judicious usage is fast becoming a tough menace. This necessitates the urgent unleashing of novel and diverse strategies and antibacterial compounds. Since fi nding a new antibiotic from the scratch, followed by endless clinical trials is exceedingly time-consuming, a powerful alternate strategy of CADD coupled with repurposing the available drugs could save precious time and money. DNA gyrases (topoisomerase II) of E.coli are among the promising new drug targets. The interface between the N-terminal domain of gyrA and C-terminal domain of gyrB which is targeted by most of the available inhibitory drugs, is of particular interest. Crucial active site residues within the N-terminal domain of gyrA were delineated through a literature search. FDA approved drugs were docked using FlexX on the receptors created around the co-crystallized reference ligand. Based on the docking scores and interactions with crucial residues, 12 leads were shortlisted, namely ceforanide, tetrahydrofolic acid, azlocillin, cefazolin, adenosine triphosphate, cefi xime, dihydronicotinamide adenine dinucleotide, moxalactam, leucal, cromoglicic acid, cefotetan, and cedax. Surprisingly quinolones, which are approved inhibitors of gyrases were not picked up in the top leads, rather, the most dominant class of molecules that docked successfully was cephalosporin. Our results indicated that these cephalosporins, as well as the other shortlisted leads, could be further optimized and validated through in-vitro experiments for their potential as gyrase A antagonists. Hence the present study holds immense promise in combating MDR of human bacterial pathogens.
ORIGINAL ARTICLE Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facili... more ORIGINAL ARTICLE Drug-resistant Escherichia coli (E. coli) has overburdened the healthcare facilities in recent years and is getting hard to combat, mandating search for novel therapeutics with a broad antibacterial spectrum and high chemotherapeutic index. The 24 kDa domain of DNA gyrase B that is involved in the ATPase activity has been reported to be a promising target for inhibitors. A PDB structure (1KZN) of the 24kD domain of gyrase B with the co-crystallized ligand clorobiocin was used for the docking studies to explore a library of 2924 FDA approved drugs from www.zinc.docking.org. FlexX docking module from Biosolve IT was used for receptor preparation and in silico docking experiments. Docking studies on the pocket created around the reference ligand clorobiocin revealed the best score with diminazene aceturate and it also demonstrated interactions with the crucial amino acids present within the pocket. Diminazene aceturate has been conventionally been used as an antiparasitic molecule in animals and it has also been demonstrated to exhibit repurposing potential in the treatment of disorders triggered due to overproduction of infl ammatory cytokines, pulmonary hypertension, ischemia-induced cardiac pathophysiology, etc. among others. Findings from this study indicate the possibility of repurposing the age-old molecule diminazene aceturate into a DNA gyrase B antagonist to combat not just the drug-resistant E. coli but also other gram-negative ESKAPE pathogens. It may also aid in alleviating the infl ammatory response induced in the body of the patients suffering from septicemia caused by a variety of Gram-negative bacterial pathogens.
The alarming multiple drug resistance developed by Escherichia coli towards the routine conventio... more The alarming multiple drug resistance developed by Escherichia coli towards the routine conventional antibiotics owing to their non-judicious usage is fast becoming a tough menace. This necessitates the urgent unleashing of novel and diverse strategies and antibacterial compounds. Since fi nding a new antibiotic from the scratch, followed by endless clinical trials is exceedingly time-consuming, a powerful alternate strategy of CADD coupled with repurposing the available drugs could save precious time and money. DNA gyrases (topoisomerase II) of E.coli are among the promising new drug targets. The interface between the N-terminal domain of gyrA and C-terminal domain of gyrB which is targeted by most of the available inhibitory drugs, is of particular interest. Crucial active site residues within the N-terminal domain of gyrA were delineated through a literature search. FDA approved drugs were docked using FlexX on the receptors created around the co-crystallized reference ligand. Based on the docking scores and interactions with crucial residues, 12 leads were shortlisted, namely ceforanide, tetrahydrofolic acid, azlocillin, cefazolin, adenosine triphosphate, cefi xime, dihydronicotinamide adenine dinucleotide, moxalactam, leucal, cromoglicic acid, cefotetan, and cedax. Surprisingly quinolones, which are approved inhibitors of gyrases were not picked up in the top leads, rather, the most dominant class of molecules that docked successfully was cephalosporin. Our results indicated that these cephalosporins, as well as the other shortlisted leads, could be further optimized and validated through in-vitro experiments for their potential as gyrase A antagonists. Hence the present study holds immense promise in combating MDR of human bacterial pathogens.
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therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some
extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the
fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting
Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19
vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then
world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19
vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine
will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include
high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline
healthcare workers and those involved in essentials industries. Various platforms for vaccine development are
available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies
for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and
hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after
Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity
and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of
this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this
novel coronavirus which has crippled the world in terms of economy, human health and life.
therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some
extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the
fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting
Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19
vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then
world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19
vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine
will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include
high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline
healthcare workers and those involved in essentials industries. Various platforms for vaccine development are
available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies
for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and
hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after
Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity
and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of
this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this
novel coronavirus which has crippled the world in terms of economy, human health and life.