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2000
Volume 32, Issue 38
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Aim

This study aimed to screen the potential phytochemicals derived from (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the host- pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular dynamics approach.

Background

The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing infection cases. Drugs and vaccines for smallpox are being used to reduce the infection. However, no specific drugs or vaccines are available to combat this infection.

Methods

The TMPK and D9 decapping enzymes were retrieved from the MPXV virus UK strain in FASTA format. Due to the unavailability of an experimentally determined structure, the 3D structure was modelled SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from using a maestro module. The potential inhibitors were examined QSAR analysis. Additionally, through MD simulation 250 ns, the stability was analyzed, and the MM-GBSA was employed to calculate the binding affinities.

Results

The molecular investigation revealed asparoside-C (PubChem ID: 158598) and asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, , tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed the ADME and QSAR analyses. Moreover, the simulation study of over 250 ns revealed strong stability, followed by RMSD, RMSF, The free energy calculation MM-GBSA exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK and the D9 decapping enzyme according to their respective scores.

Conclusion

The docking, QSAR, and simulation investigation revealed dual-target inhibitors activity of phytochemicals from towards the MPXV targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.

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Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus
Curr. Med. Chem. 32, 8678 (2025); https://doi.org/10.2174/0109298673361923250101072831
/content/journals/cmc/10.2174/0109298673361923250101072831
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  • Article Type:     Research Article
Keyword(s): Asparagus racemosus; D9 decapping enzyme; molecular docking; monkeypox virus; RMSF; thymidylate kinase

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