Exploring Dolichos lablab compounds as potential inhibitors for fusion (F) protein of human metapneumovirus (HMPV): A systematic computational approach
M. M. Hossain, Md. Jahid Hasan Apu, Md. Faisal Bin Abdul Aziz, Md. Tanzimur Rahman Tanjil, Liton Chandra Das, Antora Kar, Fatematuz Zuhura Evamoni, Md. Mahbub Morshed
Abstract
One of the most crucial respiratory pathogens in the world, namely human metapneumovirus (HMPV), causes acute upper and lower respiratory tract infection. The HMPV Fusion (F) protein is a vital element for viral entry and is the sole target of neutralizing antibodies, making it a prime target for drug and vaccine development. Targeting the Fusion (F) protein of HMPV for inhibition has emerged as a potential therapeutic strategy, particularly in respiratory infection treatment. We aimed to identify potential inhibitors against HMPV F protein by molecular docking and molecular dynamics study. Through molecular docking, we were able to identify 16 lead compounds derived from Dolichos lablab (DL). These compounds exhibited robust binding affinities with the HMPV F protein, with better docking scores compared to the ribavirin inhibitor as a control with a -6.7 kcal/mol docking score. Among these top-ranked compounds, Brassinolide (CID_115196), Quercetin (CID_5280343), and 2'-Hydroxygenistein (CID_5282074) demonstrated favorable molecular, pharmacokinetics, and drug-like properties, promising biological activities, and acceptable toxicity profiles. Furthermore, Brassinolide, Quercetin, and 2'-Hydroxygenistein were found to be promising drug inhibitors with the greatest binding stability against the HMPV F protein compared to the ribavirin inhibitor, which is validated by the highest protein-ligand interactions and lowest Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Radius of Gyration (Rg) values using 100 ns molecular dynamic simulation. Our study provides valuable insights into the therapeutic potential of DL compounds as potential or hypothetical inhibitors for HMPV F protein having three promising candidates- Brassinolide, Quercetin, and 2'-Hydroxygenistein. These results warrant further validation through detailed in vitro and in vivo investigations.