Computational investigation of binding of chloroquinone and hydroxychloroquinone against PLPro of SARS-CoV-2.

Journal of Biomolecular Structure & Dynamics
Dhaval PatelP C Jha

Abstract

Novel coronavirus SARS-CoV-2 has infected 18 million people with 700,000+ mortalities worldwide and this deadly numeric figure is rapidly rising. With very few success stories, the therapeutic targeting of this epidemic has been mainly attributed to main protease (Mpro), whilst Papain-like proteases (PLpro) also plays a vital role in the processing of replicase polyprotein. Multifunctional roles of PLpro such as viral polypeptide cleavage, de-ISGlyation and immune suppression have made it a promising drug target for therapeutic interventions. Whilst there have been a number of studies and others are on-going on repurposing and new-small molecule screening, albeit previously FDA approved drugs viz. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have only been found effective against this pandemic. Inspired by this fact, we have carried out molecular docking and dynamics simulation studies of FDA approved CQ and HCQ against SARS-CoV-2 PLpro. The end aim is to characterise the binding mode of CQ and HCQ and identify the key amino acid residues involved in the mechanism of action. Further, molecular dynamics simulations (MDS) were carried out with the docked complex to search for the conformational space and for understanding the in...Continue Reading

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Datasets Mentioned

BETA
QJA17047.1

Methods Mentioned

BETA
Ubiquitination
glycosylation
MDS
PCA

Software Mentioned

Epik
SP
GROMACS
VMD
LigPrep
gmx covar
TASSER
BIOVIA
gmx
mmpbsa

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