A dynamic simulation study of FDA drug from zinc database against COVID-19 main protease receptor

Abstract

The sudden outbreak of COVID-19 has been responsible for several deaths across the globe. Due to its high contagious nature, it spreads from one human to another very quickly. Now it becomes a global public health threat with no approved treatments. In silico techniques can accelerate the drug development process. Our research aimed to identify the novel drugs for inhibition of Main protease (Mpro) enzyme of COVID-19 by performing in silico approach. In this context, a library consisting of 3180 FDA-approved drugs from ‘the ZINC database’ was used to identify novel drug candidates against ‘the Mpro’ of SARS-CoV-2. Initially, the top 10 drugs out of 3180 drugs were selected by molecular docking according to their binding score. Among 10 selected drugs; seven drugs that showed binding with Mpro enzyme residue Glu166 were subjected to100 ns Molecular dynamics (MD) simulation. Out of seven compounds, four namely, ZINC03831201, ZINC08101052, ZINC01482077, and ZINC03830817 were found significant based on MD simulation results. Furthermore, RMSD, RMSF, RG, SASA, PCA, MMPBSA (for last 40 ns) were calculated for the 100 ns trajectory period. Currently, the world needs potent drugs in a short period and this work suggests that these four drugs could be used as novel drugs against COVID-19 and it also provides new lead compounds for further in vitro, in vivo, and ongoing clinical studies against SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• FDA drugs
• zinc database
• main protease
• molecular dynamic simulation
• molecular docking

Acknowledgements

The authors acknowledge the Department of Botany, Kumaun University, S.S.J Campus, Almora for providing basic facilities to conduct this research work. The authors also acknowledge Kumaun University, Nainital for providing high-speed internet facilities. We also extend our acknowledge to Rashtriya Uchchattar Shiksha Abhiyan (RUSA), Ministry of Human Resource Development, Government of India to provide Computational infrastructure for the establishment of the Bioinformatics Centre in Kumaun University, S.S.J Campus, Almora.

Disclosure statement

No potential conflict of interest was reported by the author(s).