An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets

Liya Thurakkal; Satyam Singh; Rajarshi Roy; Parimal Kar; Sushabhan Sadhukhan; Mintu Porel

doi:10.1016/j.cplett.2020.138193

An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets

Chem Phys Lett. 2021 Jan 16:763:138193. doi: 10.1016/j.cplett.2020.138193. Epub 2020 Nov 15.

Authors

Liya Thurakkal¹, Satyam Singh², Rajarshi Roy², Parimal Kar², Sushabhan Sadhukhan¹, Mintu Porel¹

Affiliations

¹ Discipline of Chemistry, Indian Institute of Technology Palakkad, Kerala 678 557, India.
² Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Madhya Pradesh 453 552, India.

Abstract

The emerging paradigm shift from 'one molecule, one target, for one disease' towards 'multi-targeted small molecules' has paved an ingenious pathway in drug discovery in recent years. We extracted this idea for the investigation of drugs for COVID-19. Perceiving the importance of organosulfur compounds, seventy-six known organosulfur compounds were screened and studied for the interaction with multiple SARS-CoV-2 target proteins by molecular dynamics simulation. Lurasidone and its derivatives displayed substantial binding affinity against five proteins (Mpro, PLpro, Spro, helicase and RdRp). The pharmacokinetics, ADMET properties and target prediction studies performed in this work further potentiates the effectiveness against SARS-CoV-2.

Keywords: Helicase; MM-PBSA; Main protease (Mpro); Molecular docking analysis; Molecular dynamics simulation; Multi-targeting drugs; Organosulfur compounds; Papain-like protease (PLpro); RNA-dependent RNA polymerase (RdRp); SARS-CoV-2; Spike protein (Spro).