Dataset Information

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation - Targeting Mpro and pan-coronavirus post-fusion Spike protein.

ABSTRACT:

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.

SUBMITTER: Mandal SK

PROVIDER: S-EPMC10785248 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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<i>In silico</i> anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation - Targeting Mpro and pan-coronavirus post-fusion Spike protein.

Mandal Sumit Kumar SK Rehman Md Muzaffar-Ur MM Katyal Ashish A Rajvanshi Kanishk K Kannan Manoj M Garg Mohit M Murugesan Sankaranarayanan S Deepa P R PR

Journal of traditional and complementary medicine 20230713 1

<h4>Background and aim</h4>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 ...[more]

PMID: 38223813

Similar Datasets

Project description:BackgroundNayopayam kwatha (NK) is a well-known polyherbal formulation widely used to cure respiratory ailments, heart problems, and postnatal difficulties. Literature suggests that so far no standardization protocol was developed for NK to validate its quality and purity.Objective(s)To develop a standardization protocol for NK based on the marker phytoconstituents present in the individual herbs of the formulation.Materials and methodsThe roots of bala [Sida cordifolia (B1) and Sida retusa (B2)], seeds of jeeraka (Cuminum cyminum), and rhizomes of nagara (Zingiber officinale) were the ingredients of NK. Since there were two source plants for bala, two sets of NK (NKB1 and NKB2) were prepared in the ratio 3:2:1 as per Vaidya Manorama and 10:1:1 as per Arogyaraksha Kalpadruma along with 1:1:1 as per the general way of Ayurvedic polyherbal decoctions. Both the individual herbs and the kwatha (decoction) prepared were analyzed in terms of pharmacognostical, organoleptic, and physcicochemical parameters as per the standard methods. Phytochemical analysis of the individual herbs resulted in the isolation of major phytoconstituents and the kwatha was quantified in terms of marker compounds with the aid of HPLC.ResultsHPLC quantification suggests that appreciable amount of marker phytoconstituents of individual herbs are present in the kwatha. Thus, the isolated compounds luteolin (C. cyminum), 6-gingerol (Z. officinale), β-sitosterol (S. retusa), and ecdysterone (S.cordifolia) can be used as markers to standardize NK.ConclusionCharacteristics of NK, as well as its individual drugs, were well-established. The present study of NK with respect to its phytochemistry revealed that the classical drug ratios of the polyherbal formulation are of utmost importance rather than the ingredients in equal proportion. The characterization parameters of individual herbs and kwatha described in this study may serve as a standard reference for quality control analysis of NK and the method developed in this study can be used as a reliable technique for standardization of NK to ensure the purity and quality of raw drugs used.