Issue 38, 2021

Drug repurposing and computational modeling for discovery of inhibitors of the main protease (Mpro) of SARS-CoV-2

Abstract

The main protease (Mpro or 3CLpro) is a conserved cysteine protease from the coronaviruses and started to be considered an important drug target for developing antivirals, as it produced a deadly outbreak of COVID-19. Herein, we used a combination of drug reposition and computational modeling approaches including molecular docking, molecular dynamics (MD) simulations, and the calculated binding free energy to evaluate a set of drugs in complex with the Mpro enzyme. Particularly, our results show that darunavir and triptorelin drugs have favorable binding free energy (−63.70 and −77.28 kcal mol−1, respectively) in complex with the Mpro enzyme. Based on the results, the structural and energetic features that explain why some drugs can be repositioned to inhibit Mpro from SARS-CoV-2 were exposed. These features should be considered for the design of novel Mpro inhibitors.

Graphical abstract: Drug repurposing and computational modeling for discovery of inhibitors of the main protease (Mpro) of SARS-CoV-2

Supplementary files

Article information

Article type
Paper
Submitted
21 may 2021
Accepted
25 iyn 2021
First published
02 iyl 2021
This article is Open Access
Creative Commons BY license

RSC Adv., 2021,11, 23450-23458

Drug repurposing and computational modeling for discovery of inhibitors of the main protease (Mpro) of SARS-CoV-2

J. R. A. Silva, H. G. Kruger and F. A. Molfetta, RSC Adv., 2021, 11, 23450 DOI: 10.1039/D1RA03956C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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