Repurposing drugs against the main protease of SARS-CoV-2: mechanism-based insights supported by available laboratory and clinical data

Molecular Omics
Sohini ChakrabortiNarayanaswamy Srinivasan

Abstract

The ongoing global pandemic of COVID-19 has brought life to almost a standstill with the implementation of lockdowns and social distancing as some of the preventive measures in the absence of any approved specific therapeutic interventions. To combat this crisis, research communities worldwide are falling back on the existing repertoire of approved/investigational drugs to probe into their anti-coronavirus properties. In this report, we describe our unique efforts in identifying potential drugs that could be repurposed against the main protease of SARS-CoV-2 (SARS-CoV-2 Mpro). To achieve this goal, we have primarily exploited the principles of 'neighbourhood behaviour' in the protein 3D (workflow-I) and chemical 2D structural space (workflow-II) coupled with docking simulations and insights into the possible modes of action of the selected candidates from the available literature. This integrative approach culminated in prioritizing 29 potential repurpose-able agents (20 approved drugs and 9 investigational molecules) against SARS-CoV-2 Mpro. Apart from the approved/investigational anti-viral drugs, other notable hits include anti-bacterial, anti-inflammatory, anti-cancer and anti-coagulant drugs. Our analysis suggests that som...Continue Reading

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Citations

Sep 15, 2020·Journal of Biomolecular Structure & Dynamics·Adewale Oluwaseun FadakaMervin Meyer
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Methods Mentioned

BETA
in
in silico techniques

Clinical Trials Mentioned

NCT04335123
NCT04292899
NCT04292730
NCT04349410
NCT04252664
NCT04321616
NCT04257656
NCT04323761
NCT04315948
NCT04280705

Software Mentioned

EDIA
ProBiS
Maestro GUI
Excelra
PDB2PQR
OpenBabel
MGLTools
DALI
DALI search
Promals3D

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