II 型跨膜丝氨酸蛋白酶是宿主防御病毒进入和某些癌细胞进展的有效药理学靶点。这些丝氨酸蛋白酶裂解病毒刺突蛋白，以暴露融合肽以进入细胞，这对于病毒的生命周期至关重要。 TMPRSS2 抑制剂还可以对抗利用它们进入细胞的呼吸道病毒。我们的研究结合了虚拟筛选、全原子分子动力学和良好的元动力学模拟，确定了 Vicenin-2、新橙皮苷、柚皮苷和大黄素是有前途的 TMPRSS2 拮抗剂。对于 Vicenin-2、新橙皮苷、柚皮苷和大黄素，获得的结合能分别为 - 16.3、- 15.4、- 13.6 和 - 13.8 kcal/mol。 RMSD、RMSF、PCA、DCCM 和结合自由能曲线也与这些配体在 TMPRSS2 活性位点的稳定结合相关。该研究表明，这些分子可能成为对抗未来冠状病毒和其他呼吸道病毒爆发的有前景的先导分子。© 2024。作者。

Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are - 16.3, - 15.4, - 13.6, and - 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses.© 2024. The Author(s).