Hossain Md Mainuddin, Apu Md Jahid Hasan, Aziz Md Faisal Bin Abdul, Tanjil Md Tanzimur Rahman, Das Liton Chandra, Kar Antora, Evamoni Fatematuz Zuhura, Morshed Md Mahbub
Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh.
Ministry of Public Administration, Dhaka, Bangladesh.
PLoS One. 2025 Sep 11;20(9):e0332170. doi: 10.1371/journal.pone.0332170. eCollection 2025.
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.
人类偏肺病毒（HMPV）是世界上最重要的呼吸道病原体之一，可引起急性上、下呼吸道感染。HMPV融合（F）蛋白是病毒进入细胞的关键要素，也是中和抗体的唯一靶点，因此成为药物和疫苗开发的主要目标。针对HMPV的融合（F）蛋白进行抑制已成为一种潜在的治疗策略，尤其是在呼吸道感染治疗方面。我们旨在通过分子对接和分子动力学研究来鉴定针对HMPV F蛋白的潜在抑制剂。通过分子对接，我们鉴定出了16种源自白扁豆（DL）的先导化合物。这些化合物与HMPV F蛋白表现出强大的结合亲和力，与作为对照的利巴韦林抑制剂相比，对接分数更高，后者的对接分数为-6.7 kcal/mol。在这些排名靠前的化合物中，油菜素内酯（CID_115196）、槲皮素（CID_5280343）和2'-羟基染料木素（CID_5282074）表现出良好的分子、药代动力学和类药性质，具有有前景的生物活性和可接受的毒性特征。此外，与利巴韦林抑制剂相比，油菜素内酯、槲皮素和2'-羟基染料木素被发现是有前景的药物抑制剂，对HMPV F蛋白具有最大的结合稳定性，这通过100 ns分子动力学模拟中最高的蛋白质-配体相互作用以及最低的均方根偏差（RMSD）、均方根波动（RMSF）和回转半径（Rg）值得到验证。我们的研究为DL化合物作为HMPV F蛋白潜在或假想抑制剂的治疗潜力提供了有价值的见解，其中油菜素内酯、槲皮素和2'-羟基染料木素是三个有前景的候选物。这些结果需要通过详细的体外和体内研究进一步验证。
