Binding of inhibitors to the monomeric and dimeric SARS-CoV-2 Mpro

SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral...

Full description

Saved in:
Bibliographic Details
Published in:RSC Advances 2021-01, Vol.11 (5), p.2926-2934
Main Authors: Tam, Nguyen Minh, Nam, Pham Cam, Quang, Duong Tuan, Tung, Nguyen Thanh, Vu, Van V, Ngo, Son Tung
Format: Article
Language:English
Subjects:
Binding
CAD
Chemistry
Computer aided design
Dimers
Inhibitors
Ligands
Protease
Severe acute respiratory syndrome coronavirus 2
Viral diseases
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation. In this context, our study has revealed that in silico screening for inhibitors of SARS-CoV-2 Mpro can be reliably done using the monomeric structure of the Mpro instead of the dimeric one. Docking and fast pulling of ligand (FPL) simulations for both monomeric and dimeric forms correlate well with the corresponding experimental binding affinity data of 24 compounds. The obtained results were also confirmed via binding pose and noncovalent contact analyses. Our study results show that it is possible to speed up computer-aided drug design for SARS-CoV-2 Mpro by focusing on the monomeric form instead of the larger dimeric one. Binding of inhibitors to the monomeric SARS-CoV-2 Mpro is similar to the dimeric one.
ISSN:2046-2069
2046-2069
DOI:10.1039/d0ra09858b