Videoing B and its Stereoisomers as Inhibitors of Nipah Virus- An In-silico Study of Structure-Based Virtual Screening and Comparative ADMET Profiling

Nipah virus (NiV) can cause a pandemic. Since there are no effective treatments available for NiV, the development of drugs requires immediate attention. In the context of drug discovery, natural products have emerged as a promising branch with tremendous scope. In this study, we screened 959 phytochemicals from 10 Indian medicinal plants using the IMPPAT database, PyRx, ProTox 3.0, SwissADME and AutoDock 4. Videoin B (L2) bypassed all 7 screening levels. Its stereoisomeric forms (1R,2R,4aS,6S,8aS)-2,5,5,8a-tetramethyl-5'-oxo-octahydro-2H-spiro[naphthalene-1,2'-oxolan]-6-yl acetate (L1) and (1S,2S,4aR,6R,8aR)-2,5,5,8a-tetramethyl-5'-oxo-octahydro-2H-spiro[naphthalene-1,2'-oxolan]-6-yl acetate (L3) were obtained from the LOTUS database. L1, L2 and L3 showed binding score of -6.7, -7.5 and -7.8 kcal/mol respectively, better than the standard- Ribavirin (L0) when docked with the attachment glycoprotein of NiV. The impact of stereoisomerism on inhibitory action, drug-like properties, ADMET profiles, and toxicology was thoroughly examined by using ADMETlab. Better docking scores, improved pharmacokinetics, medicinal properties, ADMET profiles and reduced toxicity concerns suggest that these three natural products- L1, L2 and L3 can be potent candidates for the novel drug discovery of Niv. Hence, this study is a step towards pandemic preparedness and aims to contribute to the drug development of deadly NiV.