Anti-HIV and anti-HCV small molecule protease inhibitors in-silico repurposing against SARS-CoV-2 M^pro for the treatment of COVID-19

Abstract

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a global health emergency warranting development and implementation of targeted treatment. The enzyme main protease (M^pro; also known as 3C-like protease) is emerging as an attractive drug target. This enzyme plays an indispensable role in processing the translated polyproteins of viral RNA. Inhibiting the activity of M^pro would wedge viral replication. To facilitate the discovery of targeted therapy for COVID-19, we carried out the structure-assisted repurposing of existing protease inhibiting small molecules to target SARS-CoV-2 M^pro. Based on the structure of SARS-CoV-2 M^pro, here we report the small drug molecule namely saquinavir as its potent inhibitor. Findings support the premise that this promising antiviral protease inhibiting small drug molecule can be validated and implemented for the treatment and clinical management of COVID-19 pandemic disease.

Communicated by Ramaswamy H. Sarma.

Keywords:

• SARS-CoV-2M^pro
• COVID-19
• pandemic
• main protease
• inhibitor

Acknowledgements

SA is grateful to SERB-DST, India for the award of JC Bose National Fellowship (SR/S2/JCB-49/2011) and to Department of Biotechnology (DBT), Governemnt of India (BT/PR12828/AAQ/1/622/2015) for financial support.

Declaration of competing interest

The author declares that there is no competing interest in this work.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.