Investigating small molecules in propolis as Nipah virus glycoprotein (NiV-G) inhibitors through molecular interaction studies

Abstract

Despite the significant fatality rates associated with Nipah virus (NiV) outbreaks in South Asia, including Bangladesh, and India, till today, there is no approved medications to treat it. In this context, small molecules in propolis were computationally screened through pharmacokinetic and toxicity studies followed by molecular docking and dynamics simulation with Nipah virus glycoprotein (NiV-G protein) to assess their anti-Nipah potential. A thorough literature analysis was performed to identify antiviral compounds in propolis from a pool of 84 experimental articles. Following ADMET analysis, 27 molecules out of 34 were docked against NiV-G and compared with a control ligand, ribavirin, which is an investigational drug against Nipah. The molecular docking revealed that bauer-7-en-3β-yl acetate (BA) and moronic acid (MA) bound more strongly to the active site of NiV-G than ribavirin and other ligands. Investigation of root-mean-square deviation (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), molecular surface area (MolSA), binding free energy (MM-PBSA), the complexity of hydrogen bonds (HBs), and secondary structure of ligand-target interactions for 100 ns by molecular dynamics (MD) simulation study further supported the docked complex's stability and compactness. Therefore, the in silico molecular interaction analysis reports that both molecules may be the possible candidates against Nipah infection.

Keywords

• Propolis
• Nipah virus (NiV)
• Nipah virus glycoprotein (NiV-G)
• Molecular dynamics simulation
• MM-PBSA