Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (M^pro) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of M^pro protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski’s rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the M^pro protein’s function and controlling viral replication.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• protease
• ursolic acid
• carvacrol
• oleanolic acid

Acknowledgements

Authors are thankful to Dr. Prashanth N Suravajhala, Birla Institute of Scientific Research (BISR). Jaipur, Rajasthan and Dr. MNV Prasad Gajula, Institute of Biotechnology, Hyderabad for critical proofreading of final manuscript. AK thanks the Director, UCB for encouragement, suggestions and timely help.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical standards

Ethical standards are compulsory for studies relating to human and animal subjects.