Biological and Medicinal Chemistry

The Natural Way Forward: Molecular Dynamics Simulation Analysis of Phytochemicals from Indian Medicinal Plants as Potential Inhibitors of SARS-CoV-2 Targets



The natural way forward: Molecular dynamics simulation analysis of phytochemicals from Indian medicinal plants as potential inhibitors of SARS-CoV-2 targets

Pratap Kumar Parida 1#, Dipak Paul 1#, Debamitra Chakravorty 2*#

1 Noor Enzymes Private Limited, 37-B, Darga Road, Kolkata - 700 017, India

2 Novel Techsciences (OPC) Private Limited, 37-B, Darga Road, 1st Floor, Kolkata - 700 017, India

* Corresponding author:

Debamitra Chakravorty, PhD (Project Lead - Computational Biology)

Novel Techsciences (OPC) Private Limited, 37-B, Darga Road, 1st Floor, Kolkata - 700 017, India

E-mail: [email protected]

#All the authors have contributed equally to the paper.


The pandemic COVID-19 has become a global panic and health issue forcing our lives towards a compromised "new normal". Research is still ongoing to develop effective antiviral drugs and vaccines against SARS-CoV-2. Thus, to address the current outbreak, development of natural inhibitors as a prophylactic measure is an attractive strategy due to their natural diversity and safety. Phytochemicals that target viral entry (Spike glycoprotein) and replication (3CLPro) are lucrative in terms of both economy and health for the treatment of the deadly virus. In this context, this work explored natural compounds from Indian medicinal plants as potential inhibitors for containing the spread SARS-CoV-2. The phytochemicals were rationally screened from 55 Indian medicinal plants in our previous work. All atom 100 ns molecular dynamics simulations were performed using high performance computing for 8 top scoring rationally screened phytochemicals from Withania somnifera and Azadirachta indica and two repurposed drugs against the spike glycoprotein and the main protease of SARS-CoV-2. MM/PBSA, Principal component analysis and hydrogen bond occupancy were analysed to characterize protein–ligand interactions and to find the binding free energy. Biological pathway enrichment analysis was also carried out to observe the therapeutic efficacy of these phytochemicals. The results revealed that Withanolide R (-141.96 KJ/Mol) and 2,3-Dihydrowithaferin A (-87.60 KJ/Mol) were with the lowest relative free energy of binding for main protease and the spike proteins respectively. It was also observed that the phytochemicals exhibit a remarkable multipotency with the ability to modulate various human biological pathways especially pathways in cancer. Conclusively we suggest that these compounds need further detailed in vivo experimental evaluation and clinical validation for implementation as potent therapeutic agent for combating SARS-CoV-2.


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