A Study of Potential SARS-CoV-2 Antiviral Drugs and Preliminary Research of Their Molecular Mechanism, Based on Anti-SARS-CoV Drug Screening and Molecular Dynamics Simulation

Xiaomeng Zhao, Ruixia Liu, Zhi Miao, Nan Ye, Wenyu Lu

10.1089/cmb.2020.0112

Research curated

Abstract

This research was based on virtual docking screening and molecular dynamics simulation among the 30 drugs analyzed, which drug had the best inhibitory effect on 3CL protease (Mpro) hydrolase. AutoDock Vina is used for molecular docking. Through our research, the binding affinity of saquinavir and raltegravir to the protein is higher than other candidate drugs in molecular docking; they are −9.1 kcal/mol and −9 kcal/mol, respectively. Among them remdesivir performance was mediocre, only −7.9 kcal/mol. In our study, ultimately, these systems are also basically stable. The overall contraction of the protein structure is most obvious after the combination of remdesivir. In the remdesivir-protein system, the structure of the terminal end has undergone relatively large changes. And the total number of hydrogen bonds formed in the remdesivir-protein system is larger. The hydrogen bonds can be maintained for a longer time, and the final interaction energy is stronger than other systems. These amino acid sequence fragments have high affinity with the remdesivir molecule. Remdesivir can change the structure of the protein to make it stronger in binding with itself through the interaction with the protein. The simulation study of drug screening for new coronaviruses can provide further support for new coronavirus effective drugs and provide powerful support to defeat the virus.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Saquinavir mesylate
Tipranavir
Fosamprenavir
Abacavir
Elvitegravir
Maribavir
Desoxyrhaponticin	Deoxyrhapontin
Sophoradin
Disulfiram
Carmofur
Ebselen
PX-12	2-(Sec-butyldisulfanyl)-1h-imidazole
Thiadiazolidinone-8	thiadiazolidinone-8 , TDZD-8, GSK3β Inhibitor I, NP 01139
Cinanserin
Polydatin	Piceid
Saquinavir
Raltegravir
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Enzaplatovir
Presatovir
Shikonin
Tideglusib
Remdesivir
Atazanavir
Carfilzomib
Ritonavir
Darunavir
Bortezomib	Velcade, Chemobort, Bortecad
Ciclosporin	cyclosporine, cyclosporin, cyclosporine A
Montelukast
Lopinavir
Indinavir

Related interactions

Target	Drug	Type	Result
3C-like protease	Saquinavir mesylate	Computational	positive
3C-like protease	Raltegravir	Computational	positive
3C-like protease	Remdesivir	Computational	positive
3C-like protease	Fosamprenavir	Computational	positive
3C-like protease	Enzaplatovir	Computational	positive
3C-like protease	Presatovir	Computational	positive
3C-like protease	Abacavir	Computational	positive
3C-like protease	Elvitegravir	Computational	positive
3C-like protease	Maribavir	Computational	positive
3C-like protease	Desoxyrhaponticin	Computational	positive
3C-like protease	Polydatin	Computational	positive
3C-like protease	Sophoradin	Computational	positive
3C-like protease	Disulfiram	Computational	positive
3C-like protease	Carmofur	Computational	positive
3C-like protease	Shikonin	Computational	positive
3C-like protease	Ebselen	Computational	positive
3C-like protease	Tideglusib	Computational	positive
3C-like protease	PX-12	Computational	positive
3C-like protease	Thiadiazolidinone-8	Computational	positive
3C-like protease	Ciclosporin	Computational	positive
3C-like protease	Cinanserin	Computational	positive
3C-like protease	Atazanavir	Computational	positive
3C-like protease	Carfilzomib	Computational	positive
3C-like protease	Bortezomib	Computational	positive
3C-like protease	Montelukast	Computational	positive