Research & Reviews: Journal of Computational Biology
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A molecular docking study and in silico analysis: targeting the marburg virus protein vp35 using active phytocompounds from alchemilla vulgaris
Abstract
Objective: The Marburg Virus Disease (MVD) is an infectious viral disease originating from African Fruit Bats (Rousettus aegyptiacus) that has become the root cause of a fatal hemorrhaging viral fever. As per reports from the WHO, MVD has claimed the lives of millions of people worldwide, with a disease fatality rate ranging from 24% in initial outbreaks to 88% in recent times owing to a difference in viral strains and epidemic management across countries. This study is an attempt to recognize the various biochemical characteristics of the phytocompounds present in Alchemilla vulgaris and document their extraordinary medicinal values as a possible source of herbal remedy to prevent or cure the Marburg Virus Disease.
Methodology: The main protein taken from the Marburg Virus for this study is the RNA binding domain VP35 protein (PDB ID: 4GH9). The 3D structure of the protein was taken from the PDB site, while the phytocompounds of Alchemilla vulgaris (133 in total) were derived from the PubChem database. After that, the protein was prepared by removing the water and heteroatom molecules, as well as ligands that showed poor binding sites. Then the molecular docking process was carried out using the PyRx tool. Finally, the drug-likeness and toxicity profiles of the top 3 best-docked phytocompounds were created through the Swiss-ADME tool, Boiled-Egg analysis, and ADMET Lab 2.0 web server.
Results: The Ramachandran Plot analysis predicted the possible conformations of the amino acid residues in the protein peptide through a graphical diagram of Phi (φ) v/s Psi (ψ) values. The results of the molecular docking process revealed that the top 3 phytocompounds of Alchemilla vulgaris showed significant binding affinities (>7 Kcal/mol) with the Marburg virus’s VP35 protein, thus conclusively preventing various biochemical processes such as proteolytic cleavage formation, and viral translation, transcription, and replication within the host cell. Additionally, the ADME profiling and toxicity prediction showed that all the top 3 phytocompounds, namely, Hypericin, Beta-Sitosterol, and Cholesterol were safe, possessing drug-like characteristics.
Conclusion: From the results of this study, it can be concluded that Hypericin, Beta-Sitosterol, and Cholesterol, the three ethnobotanical compounds of Alchemilla vulgaris, have significant finding affinity with the Marburg virus’s VP35 protein and have the potential to inhibit the development of the viral hemorrhaging fever MVD as an alternate source of its herbal remedy.
Keywords: Marburg, Marburg Virus Disease, MVD, VP35, Alchemilla vulgaris, Molecular Docking
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DOI: https://doi.org/10.37591/rrjocb.v13i2.3317
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