Drug repositioning against COVID-19: a first line treatment

Abstract

COVID-19 disease caused by the SARS-CoV-2 virus has shaken our health and wealth foundations. Although COVID-19 vaccines will become available allowing for attenuation of disease progression rates, distribution of vaccines can create other challenges and delays. Hence repurposed drugs against SARS-CoV-2 can be an attractive parallel strategy that can be integrated into routine clinical practice even in poorly-resourced countries. The present study was designed using knowledge of viral pathogenesis and pharmacodynamics of broad-spectrum antiviral agents (BSAAs). We carried out the virtual screening of BSAAs against the SARS-CoV-2 spike glycoprotein, RNA dependent RNA polymerase (RdRp), the main protease (Mpro) and the helicase enzyme of SARS-CoV-2. Imatinib (a tyrosine kinase inhibitor), Suramin (an anti-parasitic), Glycyrrhizin (an anti-inflammatory) and Bromocriptine (a dopamine agonist) showed higher binding affinity to multiple targets. Further through molecular dynamics simulation, critical conformational changes in the target protein molecules were revealed upon drug binding which illustrates the favorable binding conformations of antiviral drugs against SARS-CoV-2 target proteins. The resulting drugs from the present study in combination and in cocktails from the arsenal of existing drugs could reduce the translational distance and could offer substantial clinical benefit to decrease the burden of COVID-19 illness. This also creates a roadmap for subsequent viral diseases that emerge.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• drug repurposing
• virtual screening
• molecular dynamics simulation
• SARS-CoV-2

Acknowledgements

The schematic figure was created in BioRender.com.

Authors contribution

NB: conceived and designed the experiments, performed experiments and manuscript writing, AF and SG: made a significant contribution by performing virtual screening experiments. FA, JA, UK and TH: made a substantial contribution in revising the manuscript for intellectual content.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data and material availability

The data supporting the findings of the article are available in the Protein Data Bank (PDB) at http://www.rcsb.org. The data needed to evaluate the article is present in the article and supplementary material.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.