Expediting the drug discovery for ideal leads against SARS-CoV-2 via molecular docking of repurposed drugs

Abstract

SARS-CoV-2, the novel coronavirus spreading worldwide urges the need to repurpose drugs that can quickly enter clinical trials to combat the on-going global pandemic. A cluster of proteins are encoded for by the viral genome, each assuming a critical role in pathogen endurance inside the host. To handle the adverse circumstances, robust virtual strategies such as repurposing are coming to the fore due to being economical, efficient and rapid. Five FDA approved repurposed drugs proposed to act as inhibitors by targeting SARS-CoV-2 were used for initial evaluation via molecular docking. Moreover, a comparative analysis of the selected SARS-CoV-2 proteins against five ligands (Clemizole hydrochloride, Exemestane, Nafamostat, Pregnenolone and Umifenovir) was designed. In this regard, non-structural proteins (nsp3, nsp5, nsp10, nsp12 and nsp15), structural proteins (Spike, Nucleocapsid protein) and accessory proteins (ORF 3a, ORF 7a and ORF 9 b) were selected. Here, we aim to expedite the search for a potential drug from the five FDA approved repurposing drugs already in use for treatment of multiple diseases. Based on docking analysis, Umifenovir and Pregnenolone are suggested to show potential inhibitory effects against most of the SARS-CoV-2 proteins. These drugs are noteworthy since they exhibit high binding towards target proteins and should be used as lead compounds towards in vitro and in vivo studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• COVID-19
• docking
• nsps
• ORFs
• drug repurposing

Acknowledgements

We would also like to thank Dr. Neel S. Bhavesh for letting us use his computational facility at ICGEB, New Delhi for this study.

Disclosure statement

The authors declare that there is no conflict of interest, which could affect the publishing of this article.

Correction Statement

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

Additional information

Funding

This work was supported by the Department of Science and Technology (DST)-ECRA/2017/00012 and Department of Biotechnology (DBT)-BT/PR27444/BRB/10/1645/2018.