Virtual screening of phytochemicals by targeting multiple proteins of severe acute respiratory syndrome coronavirus 2: Molecular docking and molecular dynamics simulation studies.

OBJECTIVE: Medicinal herbs are being investigated for medicationhg development against SARS-CoV-2 as a rich source of bioactive chemicals. One of the finest approaches for finding therapeutically effective drug molecules in real time is virtual screening scheme such as molecular docking in conjunction with molecular dynamics (MD) simulation. These virtual techniques provide an ample opportunity for the screening of plausible inhibitors of SARS-CoV-2 different target proteins from a comprehensive and extensive phytochemical library. The study was designed to identify potential phytochemicals by virtual screening against different receptor proteins. METHODS: In the current study, a library of plant secondary metabolites was created by manually curating 120 phytochemicals known to have antimicrobial as well as antiviral properties. In the current study, different potential phytochemicals were identified by virtual screening against various selected receptor proteins (i.e., viral main proteases, RNA-dependent RNA polymerase (RdRp), ADP ribose phosphatase, nonstructural proteins NSP7, NSP8, and NSP9) which are key proteins responsible for transcription, replication and maturation of SARS-CoV-2 in the host. Top three phytochemicals were selected against each viral receptor protein based on their best S-scores, RMSD values, molecular interactions, binding patterns and drug-likeness properties. RESULTS: The results of molecular docking study revealed that phytochemicals (i.e., baicalin, betaxanthin, epigallocatechin, fomecin A, gallic acid, hortensin, ichangin, kaempferol, limonoic acid, myricetin hexaacetat, pedalitin, quercetin, quercitrin, and silvestrol) have strong antiviral potential against SARS-CoV-2. Additionally, the reported preeminent reliable phytochemicals also revealed toxicity by no means during the evaluation through ADMET profiling. Moreover, the MD simulation study also exhibited thermal stability and stable binding affinity of the pedalitin with SARS-CoV-2 RdRp and SARS-CoV-2 main protease which suggests appreciable efficacy of the lead optimization. CONCLUSION: The biological activity and pharmacologically distinguishing characteristics of these lead compounds also satisfied as repurposing antiviral drug contenders and are worth substantial evaluation in the biological laboratory for the recommendation of being plausible antiviral drug candidates against SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus-2 - A Surge of CoronaVirus Disease-2019: An Epidemiological Study in Coimbatore District.

Context: Coronavirus disease-2019 (COVID-19) is an ongoing pneumonia-like cluster syndrome which originated in Wuhan city of China and is still now on escalation, causing severe outbreaks all over the world. Being a ribonucleic acid (RNA) virus which has the low proofreading RNA-dependent RNA polymerase leads to many mutations and that serves as the major cause for the progress of the disease. As per the recent research works done, 99% of COVID-19 severe acute respiratory syndrome coronavirus (SARS-CoV-2) are due to pangolin-associated coronavirus which causes the super spreading events of coronavirus. SARS-CoV-2 was identified in the nasopharyngeal swabs received in the viral transport medium at optimum temperature. Materials and Methods: The tests were conducted for a time period of 1 year from July 2020 to June 2021. A total of 77,824 samples were tested in the laboratory as per ICMR guidelines using approved RNA extraction kits and polymerase chain reaction kits. Results: In the total of 77,824 samples tested in our laboratory, 14174 positives were identified. In that, about seven positive cases (0.004%) were identified in the month of July 2020 which increased to the maximum in September 2020 to about 865 positive cases (6%) which is the peak of first wave COVID-19 in Coimbatore district, Tamil Nadu. Out of 77,824 samples tested, the actual cumulative laboratory-confirmed positive cases of about 14174 were identified. In that, 7731 (55%) male positive cases were identified, 6171 (43%) female positive cases were identified, and 270 (2%) children who were below 12 years of age also were tested positive. Conclusions: The findings of the study indicated a high predominance of SARS-CoV-2 infection in the male gender population when compared to females and children below 12 years of age in Coimbatore district as of June 2021. The surge of cases was high in September 2020 as well as in May 2021, indicating the first and second wave of COVID-19.

Mutation analysis of severe acute respiratory syndrome coronavirus-2 genomic sequences in India and its geographical relations

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been spreading all over the world, including India;the virus has been classified in various clades (L, S, V, G, GH, GR, and others) on the base of mutations. India is vulnerable to the health and financial hazards of the SARS-CoV-2 infection. Even after four phases of lockdown, the number of SARS-CoV-2 infections has been increasing in India. Clinical trials for vaccine and ribonucleic acid (RNA)-dependent RNA polymerase inhibitor are going on. The study was conducted to analyze SARS-CoV-2 genomic sequences submitted from India to identify mutations and their geographical distribution. Material and Methods: Three hundred and sixty-three sequences submitted from India were archived (GISAID database), compared with reference sequence (Wuhan, China), and phylogenetic tree was prepared. Sequences with more than 1% nucleotide stretching were excluded for mutation analysis, and multiple sequence analysis for 317 sequences was done. Mutations were analyzed as per phases of lockdown and geographical distribution. Results: Clade 'GH' appears in the second and third phases of lockdown;the clade 'V' has not been reported after March 17, 2020, in India. Spike protein mutation D614G was found in 166 sequences, out of which 164 sequences show P323 L mutation of nonstructural protein 12 (nsp12). RNA-dependent RNA polymerase coding nsp12 shows 23 types of 364 amino acid mutations. Discussion and Conclusion: SARS-CoV-2 shows increasing mutations with the time and spread of the virus. The mutations in spike protein and nsp12 regions are critical for response to undergoing trials of vaccines and drugs. © 2022 Journal of the Anatomical Society of India ;Published by Wolters Kluwer - Medknow.