Traditional medicinal plants against replication, maturation and transmission targets of SARS-CoV-2: computational investigation

Abstract

COVID-19 is an infectious pandemic caused by the SARS-CoV-2 virus. The critical components of SARS-CoV-2 are the spike protein (S-protein) and the main protease (M^pro). M^pro is required for the maturation of the various polyproteins involved in replication and transcription. S-protein helps the SARS-CoV-2 to enter the host cells through the angiotensin-converting enzyme 2 (ACE2). Since ACE2 is required for the binding of SARS-CoV-2 on the host cells, ACE2 inhibitors and blockers have got wider attention, in addition to S-protein and M^pro modulators as potential therapeutics for COVID-19. So far, no specific drugs have shown promising therapeutic potential against COVID-19. The current study was undertaken to evaluate the therapeutic potential of traditional medicinal plants against COVID-19. The bioactives from the medicinal plants, along with standard drugs, were screened for their binding against S-protein, M^pro and ACE2 targets using molecular docking followed by molecular dynamics. Based on the higher binding affinity compared with standard drugs, bioactives were selected and further analyzed for their pharmacological properties such as drug-likeness, ADME/T-test, biological activities using in silico tools. The binding energies of several bioactives analyzed with target proteins were relatively comparable and even better than the standard drugs. Based on Lipinski factors and lower binding energies, seven bioactives were further analyzed for their pharmacological and biological characteristics. The selected bioactives were found to have lower toxicity with a higher GI absorption rate and potent anti-inflammatory and anti-viral activities against targets of COVID-19. Therefore, the bioactives from these medicinal plants can be further developed as phytopharmaceuticals for the effective treatment of COVID-19.

Communicated by Ramaswamy H. Sarma

Traditional medicinal plant bioactives can potentially inhibit SARS-CoV-2 protein targets. Computational investigation revealed that selected medicinal plant bioactives have the optimal pharmacological and biological activities against COVID-19.

Keywords:

• COVID-19
• SARS-CoV-2
• molecular docking
• molecular dynamics
• medicinal plants

Acknowledgments

CSIR-CFTRI for the support and infrastructure facility. We thank Dr. Laskowski (The European Bioinformatics Institute (EMBL-EBI, Cambridgeshire, UK) for his valuable suggestions and providing customized LigPlot program. We thank Professor David A. Case (Rutgers University, NJ, USA) for providing access to the latest AMBER20 software.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

PM acknowledges senior research fellowships from UGC, Government of India, and JN from DBT, Government of India. AAAS acknowledges the research grant provided by a MAHE intramural grant [grant no. MAHE/DREG/PhD/IMF/2019]. ST acknowledges the institutional grant to IBAB from the Department of IT, BT, Science and Technology, the Government of Karnataka. IBAB is also supported by DST-FIST vide sanction no SR/FST/LSI-536/2012.