Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus
Saurav Kumar Mishra1, Anshuman Chandra2, Namrata Mitra1
1Department of Bioinformatics, University of North Bengal, District-Darjeeling, Siliguri, 734013, West Bengal, India.
Aim:
This study aimed to screen the potential phytochemicals derived from Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the hostpathogen 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 via SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from Asparagus racemosus using a maestro module. The potential inhibitors were examined via 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, i.e., tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via the ADME and QSAR analyses. Moreover, the simulation study of over 250 ns revealed strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MMGBSA 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 Asparagus racemosus towards the MPXV via targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.
