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In silico modeling for quick prediction of inhibitory activity against 3CL^pro enzyme in SARS CoV diseases.

ABSTRACT: As of 2 September 2020, the 2019 novel coronavirus or SARS CoV-2 has been responsible for more than 2,56,02,665 infections and 8,52,768 deaths worldwide. There has been an urgent need of newer drug discovery to tackle the situation. Severe acute respiratory syndrome-associated coronavirus 3C-like protease (or 3CL^pro) is a potential target as anti-SARS agents as it plays a vital role in the viral life cycle. This study aims at developing a quantitative structure-activity relationship (QSAR) model against a group of 3CL^pro inhibitors to study their structural requirements for their inhibitory activity. Further, molecular docking studies were carried out which helped in the justification of the QSAR findings. Moreover, molecular dynamics simulation study was performed for selected compounds to check the stability of interactions as suggested by the docking analysis. The current QSAR model was further used in the prediction and screening of large databases within a short time.Communicated by Ramaswamy H. Sarma.

SUBMITTER: De P

PROVIDER: S-EPMC7544940 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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In silico modeling for quick prediction of inhibitory activity against 3CLpro enzyme in SARS CoV diseases.

De Priyanka P Bhayye Sagar S Kumar Vinay V Roy Kunal K

Journal of biomolecular structure & dynamics 20200921 3

As of 2 September 2020, the 2019 novel coronavirus or SARS CoV-2 has been responsible for more than 2,56,02,665 infections and 8,52,768 deaths worldwide. There has been an urgent need of newer drug discovery to tackle the situation. Severe acute respiratory syndrome-associated coronavirus 3C-like protease (or 3CLpro) is a potential target as anti-SARS agents as it plays a vital role in the viral life cycle. This study aims at developing a quantitative structure-activity relationship ( ...[more]

PMID: 32954984

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Project description:BackgroundSevere acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations.MethodsFor this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CLpro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements.ResultsOur results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CLpro enzyme, which regulates viral replication machinery.ConclusionsOverall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.

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In silico modeling for quick prediction of inhibitory activity against 3CL^pro enzyme in SARS CoV diseases.

Publications

<i>In silico</i> modeling for quick prediction of inhibitory activity against 3CL<sup>pro</sup> enzyme in SARS CoV diseases.

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