Title:Determination of Binding Potential of HCV Protease Inhibitors Against to SARS-CoV-2 Papain-like Protease wtih Computational Docking
Volume: 18
Issue: 10
Author(s): Zihni Onur Çalışkaner*
Affiliation:
- Bioengineering Department, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul,Turkey
Keywords:
Covid-19, SARS-CoV-2, docking, protease inhibitors, drug repurposing, PLpro.
Abstract:
Background: SARS-CoV-2, a novel coronavirus that caused a pandemic respiratory disease,
has recently emerged from China. Since it is a life-threatening virus, investigation of curative
medications along with protective vaccines still maintains its importance. Drug repurposing is a reasonable
and immediate approach to combat SARS-CoV-2 infection by identifying inhibitory molecules
from marketed drugs. PL protease (PLpro) is one of the essential enzymes for the progression of
SARS-CoV-2 replication and life cycle.
Objective: We aimed to investigate the potential of 4 HCV protease inhibitors as probable repurposing
drugs in Covid-19 treatment.
Methods: In order to understand possible binding affinity of HCV protease inhibitors, Boceprevir,
Grazoprevir, Simeprevir, and Telaprevir, against PLpro, we performed docking analysis in silico.
Docking study was accomplished using AutoDock 4.2 Software. Potential druggable pockets on
PLpro were predicted by DoGSiteScorer tool in order to explore any overlapping with binding regions
and these pockets.
Results: This analysis demonstrated Boceprevir, Grazoprevir, Simeprevir and Telaprevir interacted
by PLpro with binding energies (kcal/mol) of -4.97, -4.24, -6.98, -1.08, respectively. Asn109, one of
the interacted residues with both Boceprevir and Simeprevir, is a neighbouring residue to catalytic
Cys111. Additionally, Telaprevir notably interacted with catalytic His272 in the active site.
Conclusion: Present study explains the binding efficiency and repurposing potential of certain HCV
protease inhibitors against to SARS-CoV-2 PLpro enzyme. Docking sites and potential druggability of
ligands were also crosschecked by the estimation of druggable pockets. Thereby our results can promote
promising preliminary data for research on drug development in the fight of Covid-19.