Virtual Screening, Molecular Docking and In silico ADME-Tox Analysis for Identification of Potential Main Protease (Mpro) Enzyme Inhibitors

Author(s): Debadash Panigrahi*, Ganesh Prasad Mishra

Journal Name: Anti-Infective Agents
Formerly Anti-Infective Agents in Medicinal Chemistry

Volume 19 , Issue 4 , 2021


Article ID: e130621188860
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Abstract:

Objective: Recent pandemic caused by the SARS-CoV-2, first described in Wuhan city of China in December 2019, spread widely in almost all the countries of the world. Coronavirus (COVID-19) led to the unexpected death of many people and caused a severe economic loss in a number of countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET studies are some of the effective tools for the identification of small molecules as novel antiviral drugs to treat diseases.

Methods: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of the COVID-19 pandemic. Interestingly, some compounds have been identified as possible anti-covid-19 agents for future research. A total of 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values.

Results: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best-docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and showed excellent results. All the 10 screened compounds showed a significant binding pose with the target main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties.

Conclusion: Based on these results, it is suggested that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can further be evaluated for in vitro activity, preclinical, clinical studies, and formulated in a suitable dosage form to maximize their bioavailability.

Keywords: Virtual screening, molecular docking, ADME-Tox study, COVID-19, mpro enzyme, V-Life MDS.

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Article Details

VOLUME: 19
ISSUE: 4
Year: 2021
Published on: 08 December, 2020
Article ID: e130621188860
Pages: 17
DOI: 10.2174/2211352518999201208201854
Price: $25

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