Natural compounds from Clerodendrum spp. as possible therapeutic candidates against SARS-CoV-2: An in silico investigation

Abstract

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has rattled global public health, with researchers struggling to find specific therapeutic solutions. In this context, the present study employed an in silico approach to assess the inhibitory potential of the phytochemicals obtained from GC-MS analysis of twelve Clerodendrum species against the imperative spike protein, main protease enzyme M^pro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. An extensive molecular docking investigation of the phytocompounds at the active binding pockets of the viral proteins revealed promising inhibitory potential of the phytochemicals taraxerol, friedelin and stigmasterol. Decent physicochemical attributes of the compounds in accordance with Lipinski’s rule of five and Veber’s rule further established them as potential therapeutic candidates against SARS-CoV-2. Molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy estimation revealed that taraxerol was the most promising candidate displaying the highest binding efficacy with all the concerned SARS-CoV-2 proteins included in the present analysis. Our observations were supported by robust molecular dynamics simulations of the complexes of the viral proteins with taraxerol for a timescale of 40 nanoseconds. It was striking to note that taraxerol exhibited better binding energy scores with the concerned viral proteins than the drugs that are specifically targeted against them. The present results promise to provide new avenues to further evaluate the potential of the phytocompound taraxerol in vitro and in vivo towards its successful deployment as a SARS-CoV-2 inhibitor and combat the catastrophic COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• Clerodendrum spp
• molecular docking
• drug-likeness
• MM-GBSA
• taraxerol
• molecular dynamics simulations

Acknowledgements

PK acknowledges University of North Bengal for providing fellowship to execute this work. AR, NRS and BS acknowledge Lovely Professional University, India for providing the necessary infrastructure facility. AS and PK acknowledge University of North Bengal, India for the infrastructure support to the work. The authors thank Dr. Devashan Naidoo (Centre for Algal Biotechnology, Faculty of Natural Sciences, Mangosuthu University of Technology, South Africa) for critical reading of the manuscript and thorough language correction. We also thank the anonymous reviewers for their suggestions which helped to improve the manuscript.

Disclosure statement

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