Potential anti-viral activity of approved repurposed drug against main protease of SARS-CoV-2: an in silico based approach

Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which was first reported in Wuhan province of China, has become a deadly pandemic causing alarmingly high morbidity and mortality. In the absence of new targeted drugs and vaccines against SARS-CoV-2 at present, the choices for effective treatments are limited. Therefore, considering the exigency of the situation, we focused on identifying the available approved drugs as potential inhibitor against the promising Coronavirus drug target, the Main Protease, using computer-aided methods. We created a library of U. S. Food and Drug Administration approved anti-microbial drugs and virtually screened it against the available crystal structures of Main Protease of the virus. The study revealed that Viomycin showed the highest -CDocker energy after docking at the active site of SARS-CoV-2 Main Protease. It is noteworthy that Viomycin showed higher -CDocker energy as compared to the drugs currently under clinical trial for SARS-CoV-2 treatment viz. Ritonavir and Lopinavir. Additionally, Viomycin formed higher number of H-bonds with SARS-CoV-2 Main Protease than its co-crystallised inhibitor compound N3. Molecular dynamics simulation further showed that Viomycin embedded deeply inside the binding pocket and formed robust binding with SARS-CoV-2 Main Protease. Therefore, we propose that Viomycin may act as a potential inhibitor of the Main Protease of SARS-CoV-2. Further optimisations with the drug may support the much-needed rapid response to mitigate the pandemic.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• COVID-19
• M^pro
• viomycin
• docking
• molecular dynamics
• FDA approved drugs

Acknowledgements

The authors would like to thank Mr. Pratik Chowdhury for his assistance in language editing of the manuscript.

Disclosure statement

The authors declare no competing interests.

Author contributions

SM and BG designed the experiments. SM, PC, NG, NG and BG performed the experiments, DC, PB and AKB coordinated the work. PC, NG, DB, RG. and BG prepared the manuscript. All of the authors read and approved the final manuscript.

Funding

The study was not funded by any funding agencies.