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

Graphical abstract

Highlights

• •

  This paper  in-silico identifies multifaceted inhibitors (Lurasidone and Lurasidone exo) for SARS-CoV-2 that can act through the “ one drug multiple targets” strategy.

• •

  Molecular Dynamics simulation study reveals a significantly strong binding affinity of Lurasidone and its derivative against multiple SARS-CoV-2 targets namely, main protease, papain-like protease, spike protein, RNA dependent RNA polymerase and helicase.

• •

  Lurasidone and Lurasidone exo possess favourable pharmacokinetic properties based on Lipinski’s rule, ADMET and target prediction studies.

• •

  The unique multitargeting feature of Lurasidone and Lurasidone exo warrants further  in-vitro  and  in-vivo  experiments on SARS-CoV-2 for clinical applications.

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.