Determination of Binding Potential of HCV Protease Inhibitors Against to SARS-CoV-2 Papain-like Protease wtih Computational Docking

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, PL^pro.

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 (PL^pro) 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 PL^pro, we performed docking analysis in silico. Docking study was accomplished using AutoDock 4.2 Software. Potential druggable pockets on PL^pro 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 PL^pro 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 PL^pro 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.

Cite this article as:

Çalışkaner Onur Zihni*, Determination of Binding Potential of HCV Protease Inhibitors Against to SARS-CoV-2 Papain-like Protease wtih Computational Docking, Letters in Drug Design & Discovery 2021; 18 (10) . https://dx.doi.org/10.2174/1570180818666210531092605