Comparative Docking Analysis of Rational Drugs Against COVID-19 Main Protease

LALIT SAMANT, Vyomesh Javle

10.26434/chemrxiv.12136002.v1

Research curated

Abstract

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available, and investigations regarding COVID-19 treatment are lacking. Crystallised COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess drugs found in literature as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The docking was cross-validated using Swiss Dock. COVID-19 Mpro was docked with several compounds, and docking was analysed by Biovia Discovery Studio 2020. Quinine and hydroxychloroquine were used as standards for comparison. The binding energies obtained from the docking of 6LU7, 2GTB with screened drugs viz., Quinine, Artesunate, Clotrimazol, Artemether, Quercetin, Mefloquine, ciprofloxacin, clindamycin, cipargamin, SJ-733 were in between -7.0 to -9.6 kcal/mol. On consideration of similar binding energy obtained from Autodock vina and SWISSDock and interaction residue pattern specifically (GLU 166,CYS 145, CYS44 and MET 49 residue) for SJ-733 & JPC-3210 may represent potential treatment options, and appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use against CoV.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Ciprofloxacin
Clindamycin
Cipargamin
SJ-733
Mefloquine hydrochloride
Quercetin
Artemether
Clotrimazole
Quinine
Artesunate
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b

Related interactions

Target	Drug	Type	Result
3C-like protease	Quinine	Computational	positive
3C-like protease	Mefloquine hydrochloride	Computational	positive
3C-like protease	Ciprofloxacin	Computational	positive
3C-like protease	Clindamycin	Computational	positive
3C-like protease	Cipargamin	Computational	positive
3C-like protease	SJ-733	Computational	positive
3C-like protease	Quercetin	Computational	positive
3C-like protease	Artemether	Computational	positive
3C-like protease	Clotrimazole	Computational	positive
3C-like protease	Artesunate	Computational	positive