Discovery of potential drug-like compounds against Viral protein (VP40) of Marburg Virus using pharmacophoric based virtual screening from ZINC database

ABSTRACT Marburg virus (MARV) has been confirmed to cause extreme hemorrhagic fever (HFM) in human and animals. The effective and suitable vaccine to treat the MARV virus is not commercialized in public and demands rigorously tested on several scales. This research used a CADD (Computer-Aided Drug Design) computational based technology to find novel drug-like compounds that could inhibit the replicating of the VP40. The pharmacophoric features bases screening was done using an online computational based software, “ZINC Pharmer”. We retrieved about 32456 compounds mainly focused on the properties of pharmacophores from the ZINC database. Lipinski’s rule was also used to predict these drug-like compounds. as well as molecular coupling-dependent screening and selection of VP40 screening ligand complexes based on S-rank (lower than reference) and value of root, mean square (RMSD) (bottom) to examine for reference) using the Molecular Working Environment (MOE) machine. As a result, 100 compounds were found to have a close interaction with MARV VP40, followed by the Binding energy (BE) analysis of these 100 compounds. Only 50 were the strongest binding energy than favipiravir [reference inhibitor] after using the MOE-LigX algorithm to compare their binding energy. After that, ADMET analysis predicted only five compounds (ZINC95457352, ZINC38752258, ZINC38752253, ZINC39272175, and ZINC38752377) passed the ADMET parameters and have the strongest inhibitory effect against the MARV’s VP40. It has been suggested that these “drug-like” candidates have an increased ability to inhibit MARV replication, leading to treatment of MARVD.