September 12, 2025PLoS ONE10 citationsOpen Access

Exploring Dolichos lablab compounds as potential inhibitors for fusion (F) protein of human metapneumovirus (HMPV): A systematic computational approach

MHM. M. HossainMawlana Bhashani Science and Technology University MAMd. Jahid Hasan ApuMinistry of Public Administration MAMd. Faisal Bin Abdul AzizUniversiti Putra Malaysia

Key Points

Top-ranked compounds from Dolichos lablab show strong binding to HMPV fusion protein, indicating therapeutic potential.
Brassinolide, Quercetin, and 2’-Hydroxygenistein demonstrated better binding stability than ribavirin, with favorable drug-like properties.
Molecular docking and dynamics studies reveal promising interactions and stability against HMPV's fusion protein across 100 ns simulations.
The findings highlight the importance of exploring Dolichos lablab compounds for developing effective treatments for respiratory infections.

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 (CID₁15196), Quercetin (CID₅280343), and 2’-Hydroxygenistein (CID₅282074) 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.

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