Structure-Based Virtual Screening of Phytochemicals from Phyllanthus Amarus as Potent Inhibitory Phytocompounds Against Marburg Virus Disease

Marburg virus is a deadly and highly contagious pathogen, infects both human and non-human primates, and causes life-threatening Marburg virus disease. So far, there have been 14 MAVD outbreaks since August 1967. Influenza-like illness, manifestations related to abdomen, hemorrhagic, respiratory, and vascular system are among the signs and symptoms of MVD. The protein VP 35 is a multifunctional viral protein and binds to the double-strand RNA through its RBD and masks the dsRNA, which is a key sign of virus infection, recognized by host proteins including RIG-I and MDA-5. Here, we have performed molecular docking and MD simulation studies and shown that that phytochemicals stigmasterol (ΔG = -8.62 kcal/mol) and methyl ursolate (ΔG = -9.29 kcal/mol) isolated from Phyllanthus amarus showed biologically significant poses to block the binding site of VP35 protein. The MD simulation result analysis confirmed that the complex structure of stigmasterol with RBD of protein VP35 show stable conformational dynamics during the MD simulation while methyl ursolate shows certain fluctuations in RMSD at certain time point but later attain stability. Hence, Phyllanthus amarus, which contains multiple antiviral and antimicrobial phytochemicals could be a conceivable candidate in the search for a drug for the MVD.

Keywords: MVD, MARV, VP35, RBD, Molecular Docking, MDS