Repurposing of anticancer phytochemicals for identifying potential fusion inhibitor for SARS-CoV-2 using molecular docking and molecular dynamics (MD) simulations

Abstract

The viral particle, SARS-CoV-2 is responsible for causing the epidemic of Coronavirus disease 2019 (COVID-19). To combat this situation, numerous strategies are being thought for either creating its antidote, vaccine, or agents that can prevent its infection. For enabling research on these strategies, several target proteins are identified where, Spike (S) protein is of great potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for entering the cell. S-protein is a large protein and a portion of it designated as a receptor-binding domain (RBD) is the key region that interacts with ACE2, following to which the viral membrane fuses with the alveolar membrane to enter the human cell. The hypothesis is to identify molecules from the pool of anticancer phytochemicals as a lead possessing the ability to interact and mask the amino acids of RBD, making them unavailable to form associations with ACE2. Such a molecule is termed as ‘fusion inhibitor’. We hypothesized to identify fusion inhibitors from the NPACT library of anticancer phytochemicals. For this, all the molecules from the NPACT were screened using molecular docking, the five top hits (Theaflavin, Ginkgetin, Ursolic acid, Silymarin and Spirosolane) were analyzed for essential Pharmacophore features and their ADMET profiles were studied following to which the best two hits were further analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals containing anticancer properties to serve as fusion inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2 novel coronavirus
• Fusion Inhibitors
• anticancer phytochemical repurposing
• NPACT
• Molecular Dynamics (MD) simulation

Acknowledgements

The authors gratefully acknowledge the Department of Botany, Bioinformatics and Climate Change Impacts Management, Gujarat University for providing an opportunity to access the bioinformatics research facilities.

Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Disclosure statement

The authors declare that they have no conflict of interest.

Author approvals

All authors have seen and approved the manuscript, and that it hasn't been accepted or published elsewhere

Authors contributions

CP, DG and SP conceptualized and designed the project. CP and SP developed methodology. CP and DG acquired data and wrote the manuscript. CP and DG analyzed and interpreted data. HP provided technical support. HP supervised the study. The whole manuscript was approved by all authors.

Additional information

Funding

The Financial Assistance Programme – Department of Science and Technology [Grant number GSBTM/MD/JDR/1409/2017-18] and Gujarat Council on Science and Technology [GUJCOST/Supercomputer/2019-20/1359] had provided grants for the purchase of computer hardware only and is been used up. The research work is not been granted from any fund.