SARS-CoV Mpro inhibitory activity of aromatic disulfide compounds: QSAR model

Andrey A Toropov; Alla P Toropova; Aleksandar M Veselinović; Danuta Leszczynska; Jerzy Leszczynski

doi:10.1080/07391102.2020.1818627

SARS-CoV M^pro inhibitory activity of aromatic disulfide compounds: QSAR model

J Biomol Struct Dyn. 2022 Feb;40(2):780-786. doi: 10.1080/07391102.2020.1818627. Epub 2020 Sep 9.

Authors

Andrey A Toropov¹, Alla P Toropova¹, Aleksandar M Veselinović², Danuta Leszczynska³, Jerzy Leszczynski⁴

Affiliations

¹ Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Science, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
² Faculty of Medicine, Department of Chemistry, University of Niš, Niš, Serbia.
³ Departments of Civil and Environmental Engineering, Jackson State University, Jackson, MS, USA.
⁴ Interdisciplinary Center for Nanotoxicity, Jackson State University, Jackson, MS, USA.

Abstract

The main protease (M^pro) of SARS-associated coronavirus (SARS-CoV) had caused a high rate of mortality in 2003. Current events (2019-2020) substantiate important challenges for society due to coronaviruses. Consequently, advancing models for the antiviral activity of therapeutic agents is a necessary component of the fast development of treatment for the virus. An analogy between anti-SARS agents suggested in 2017 and anti-coronavirus COVID-19 agents are quite probable. Quantitative structure-activity relationships for SARS-CoV are developed and proposed in this study. The statistical quality of these models is quite good. Mechanistic interpretation of developed models is based on the statistical and probability quality of molecular alerts extracted from SMILES. The novel, designed structures of molecules able to possess anti-SARS activities are suggested. For the final assessment of the designed molecules inhibitory potential, developed from the obtained QSAR model, molecular docking studies were applied. Results obtained from molecular docking studies were in a good correlation with the results obtained from QSAR modeling.

Keywords: Coronavirus; Monte Carlo method; Severe Acute Respiratory Syndrome; anti-SARS agents; index of ideality of correlation; molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Disulfides
Humans
Molecular Docking Simulation
Protease Inhibitors / pharmacology
Quantitative Structure-Activity Relationship
SARS-CoV-2
Severe acute respiratory syndrome-related coronavirus*

Substances

Disulfides
Protease Inhibitors

Grants and funding

A.A.T and A.P.T. are grateful for the contribution of the project LIFE-VERMEER contract (LIFE16 ENV/IT/000167) for the support. A.M.V. would like to thank the Ministry of Education and Science, the Republic of Serbia, under Project Number 172044. J.L. and DL would like to thank the NSF-CREST program for the support (grant HRD #154774).