Structure-based pharmacophore modeling, molecular docking and ADMET analysis to discover potential hMPV inhibitors

Viral infections and diseases have been causing great damage to humans for a very long time. One such infection that has surfaced recently is the human metapneumovirus (hMPV), for which there are no approved drug candidates. The current investigation aims at finding novel probable inhibitors to hMPV targeting RNA-dependent RNA polymerase (PDB ID: 8FPJ ) in complex with MRK-1 inhibitor (hereinafter regarded as reference compound, ref). A pharmacophore model was correspondingly generated and then mapped against databases such as MolPort, ChemDiv (2015), ChemSpace, and Zinc purchasable. The compounds that have mapped to the pharmacophore features consisting of three aromatic features, one hydrogen bond donor, and one hydrogen bond acceptor are upgraded for molecular docking studies. Two compounds that have demonstrated lower binding energy score than the ref compound are studied in detail for their ADMET properties. In order to ensure the results the molecular docking was performed employing SwissDock and PyRx. The ADMET analysis were executed with SwissADME and pkCSM. From these findings, the current study proposes two potential inhibitors, MCULE-2260056363 (hit1) and MCULE-5562007026 (hit2) as plausible hMPV inhibitors.