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Discovery of novel inhibitors of SARS-CoV-2 main protease.

ABSTRACT: Corona Virus Disease 2019 (COVID-19), referred to as 'New Coronary Pneumonia', is a type of acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. M^pro is one of the main targets for treating COVID-19. The current research on M^pro mainly focuses on the repurposing of old drugs, and there are only a few novel ligands that inhibit M^pro. In this research, we used computational free energy calculation to screen a compound library against M^pro, and discovered four novel compounds with the two best compounds (AG-690/13507628 and AG-690/13507724) having experimental measured IC₅₀ of just under 3 μM and low cell toxicity. Detailed decomposition of the interactions between the inhibitors and M^pro reveals key interacting residues and interactions that determine the activity. The results from this study should provide a basis for further development of anti-SARS-CoV-2 drugs.Communicated by Ramaswamy H. Sarma.

SUBMITTER: Zheng L

PROVIDER: S-EPMC8436407 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Discovery of novel inhibitors of SARS-CoV-2 main protease.

Zheng Lei L Chen Yanmei Y Bao Jingxiao J He Liping L Dong Suzhen S Qi Yifei Y Zhang John Z H JZH

Journal of biomolecular structure & dynamics 20210902 23

Corona Virus Disease 2019 (COVID-19), referred to as 'New Coronary Pneumonia', is a type of acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Mpro is one of the main targets for treating COVID-19. The current research on Mpro mainly focuses on the repurposing of old drugs, and there are only a few novel ligands that inhibit Mpro. In this research, we used computational free energy calculation to screen ...[more]

PMID: 34472424

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