In Silico Exploration of the Molecular Mechanism of Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2's Main Protease.
J Phys Chem Lett
; 11(11): 4413-4420, 2020 Jun 04.
Article
in English
| MEDLINE | ID: covidwho-258961
ABSTRACT
Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well-calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the mechanism of binding between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. By combining the existing experimental results with our computational ones, we revealed an important ligand binding mechanism of the Mpro, demonstrating that the binding stability of a ligand inside the Mpro pocket can be significantly improved if part of the ligand occupies its so-called "anchor" site. Along with the highly potent drugs and/or molecules (such as nelfinavir) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Protease Inhibitors
/
Cysteine Endopeptidases
/
Viral Nonstructural Proteins
/
Coronavirus Infections
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2020
Document Type:
Article
Affiliation country:
Acs.jpclett.0c00994
Similar
MEDLINE
...
LILACS
LIS