Identifying the natural compound Catechin from tropical mangrove plants as a potential lead candidate against 3CL^pro from SARS-CoV-2: An integrated in silico approach

Abstract

SARS-CoV-2, a member of beta coronaviruses, is a single-stranded, positive-sense RNA virus responsible for the COVID-19 pandemic. With global fatalities of the pandemic exceeding 4.57 million, it becomes crucial to identify effective therapeutics against the virus. A protease, 3CL^pro, is responsible for the proteolysis of viral polypeptides into functional proteins, which is essential for viral pathogenesis. This indispensable activity of 3CL^pro makes it an attractive target for inhibition studies. The current study aimed to identify potential lead molecules against 3CL^pro of SARS-CoV-2 using a manually curated in-house library of antiviral compounds from mangrove plants. This study employed the structure-based virtual screening technique to evaluate an in-house library of antiviral compounds against 3CL^pro of SARS-CoV-2. The library was comprised of thirty-three experimentally proven antiviral molecules extracted from different species of tropical mangrove plants. The molecules in the library were virtually screened using AutoDock Vina, and subsequently, the top five promising 3CL^pro-ligand complexes along with 3CL^pro-N3 (control molecule) complex were subjected to MD simulations to comprehend their dynamic behaviour and structural stabilities. Finally, the MM/PBSA approach was used to calculate the binding free energies of 3CLpro complexes. Among all the studied compounds, Catechin achieved the most significant binding free energy (−40.3 ± 3.1 kcal/mol), and was closest to the control molecule (−42.8 ± 5.1 kcal/mol), and its complex with 3CL^pro exhibited the highest structural stability. Through extensive computational investigations, we propose Catechin as a potential therapeutic agent against SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• COVID-19
• 3CL^pro
• virtual Screening
• MD simulation
• MM/PBSA

Acknowledgements

Dr. Amit Kumar Singh thanks Indian Council of Medical Research (ICMR) and Indian National Science Academy (INSA), New Delhi, India. Gizachew Muluneh Amera thanks the College of Natural Science, Wollo University, Dessie, Ethiopia for the sponsorship. Dr. Amit Kumar Singh, Dr. J. Muthukumaran and Dr. Monika Jain thanks Sharda University for support. Dr. A. Parthiban and Dr. V. Sachithanandam thank the Director of the National centre for Sustainable Coastal Management (NCSCM) and the NCSCM publication committee members who reviewed our article and made a recommendation for publication (NCSCM contribution Number: NCSCM/PUB/2021/0005). Views expressed are of the authors only and not necessarily of the affiliated organizations.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.