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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Coumarins and Quinolones as Effective Multiple Targeted Agents Versus Covid-19: An In Silico Study

Author(s): Mojgan Nejabat, Razieh Ghodsi* and Farzin Hadizadeh*

Volume 18 , Issue 2 , 2022

Published on: 08 February, 2021

Page: [220 - 237] Pages: 18

DOI: 10.2174/1573406417666210208223924

Price: $65

Abstract

Background: The Covid-19 virus emerged a few months ago in China, and infections rapidly escalated into a pandemic.

Objective: To date, there is no selective antiviral agent for the management of pathologies associated with covid-19 and the need for an effective agent against it is essential.

Methods: In this work, two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). Chloroquine, a reference drug without a clear mechanism against coronavirus was also docked on mentioned targets and the binding affinities compared with title compounds.

Results: The best compounds of synthetic coumarins and quinolines for each target were determined. All compounds against all targets showed binding affinity between -5.80 to -8.99 kcal/mol in comparison with the FDA-approved drug, Chloroquine, with binding affinity of -5.7 to -7.98 kcal/mol. Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets – S2, TMPRSS2 and furin – simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol. In silico ADME studies also confirmed good oral absorption for them. Furthermore, PASS prediction was calculated and coumarin-24 had higher probable activity (Pa) than probable inactivity (Pi) with acceptable protease inhibitory as well as good antiviral activity against Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and influenza.

Conclusion: Quinoline-1 and Coumarin-24 have the potential to be used against Covid-19. Hence these agents could be useful in combating covid-19 infection after further in vitro and in vivo studies.

Keywords: Covid-19, coumarins, quinolines, docking, TMPRSS2, furin, protease, spike, chloroquine.

Graphical Abstract
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