In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein
Authors
Sumit Mandal
aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
MD Rehman
bMedicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani, 333031, Rajasthan, India
Ashish Katyal
aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
Kanishk Rajvanshi
aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
Manoj Kannan
aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
Mohit Garg
dDepartment of Chemical Engineering, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani, 333031, Rajasthan, India
Sankaranarayanan Murugesan
bMedicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani, 333031, Rajasthan, India
PR Deepa
aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
Background and aim
Novel nature of the viral pathogen SARS-CoV-2 and the absence of standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe and effective remedy, for which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system of medicine was evaluated here using a combination of computational approaches, to identify potential inhibitors against two anti-SARS-CoV-2 targets – post-fusion Spike protein (structural protein) and main protease (Mpro, non-structural protein).
Experimental procedure
We docked 32 phytochemicals from the poly-herbal formulation against viral post-fusion Spike glycoprotein and Mpro followed by molecular dynamics using Schrodinger software. Drug-likeness analysis was performed using machine learning (ML) approach and pkCSM.
Results
The binding affinity of the phytochemicals in Kabasura Kudineer revealed the following top-five bioactives: Quercetin > Luteolin > Chrysoeriol > 5-Hydroxy-7,8-Dimethoxyflavone > Scutellarein against Mpro target, and Gallic acid > Piperlonguminine > Chrysoeriol > Elemol > Piperine against post-fusion Spike protein target. Quercetin and Gallic acid exhibited binding stability in complexation with their respective viral-targets and favourable free energy change as revealed by the molecular dynamics simulations and MM-PBSA analysis. In silico predicted pharmacokinetic profiling of these ligands revealed appropriate drug-likeness properties.
Conclusion
These outcomes provide: (a) potential mechanism for the anti-viral efficacy of the indigenous Siddha formulation, targeting Mpro and post-fusion Spike protein (b) top bioactive lead-molecules that may be developed as natural product-based anti-viral pharmacotherapy and their pleiotropic protective effects may be leveraged to manage co-morbidities associated with COVID-19.
Keywords: iddha medicine, Kabasura kudineer, COVID-19, SARS-CoV-2, Molecular docking, Dynamics, Post fusion spike protein, Mpro
Author Biography
Manoj Kannan, aDepartment of Biological Sciences, Birla Institute of Technology & Science (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India
cPlaksha University, SAS Nagar, Mohali, 140306, Punjab, India
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