Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

Abstract

Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• SARS-CoV-2
• ZINC database
• inhibitors
• docking
• MD simulations
• MM-GBSA

Acknowledgements

One of the authors, Durgesh Kumar (DK) thankfully acknowledges the guidance provided by Prof. B. Jayaram, Incharge, SCFBio, Indian Institute of Technology, New Delhi, India and also for providing facilities and training; and also thankful to the Department of Chemistry, University of Delhi, Delhi, India for providing facilities to purse his research work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Durgesh Kumar (DK) thankfully acknowledges to Council of Scientific and Industrial Research (CSIR, Reference no. 08/593/0002/2015/EMR I) for the fellowship. Another author, Prof. Ramesh Chandra (RC) thankfully acknowledges the financial assistance provided by the University of Delhi under DST-PURSE grant, Council of Scientific and Industrial Research (CSIR, Reference no. 02/265/16/EMR II), SERB-DST (Reference no. EEQ/2016/00489), Government of India.