Department of Pharmacy, University of Salerno, Fisciano, Italy.
Department of Pharmacy, Scuola di Specializzazione in Farmacia Ospedaliera, University of Salerno, Italy.
J Pept Sci. 2024 Dec;30(12):e3645. doi: 10.1002/psc.3645. Epub 2024 Jul 18.
Feline immunodeficiency virus (FIV) shares structural similarities with human immunodeficiency virus (HIV): the surface glycoprotein gp36 corresponds to the HIV gp41, which drives virus-host cell interactions and is targeted by the peptide entry inhibitor enfuvirtide. Following a similar drug design strategy for the development of an anti-FIV therapy, the present study investigates gp36 NHR, a peptide sequence derived from a region of gp36 that was previously found to interfere with the antiviral activity of the peptide C8, which instead derives from the gp36 MPER. CD, NMR, and MD simulations were employed to probe the conformational characteristics of gp36 NHR in the membrane-mimicking environment of SDS micelles. Our data show that gp36 NHR is characterized by three dynamic helix structures. MD simulations involving gp36 NHR, C8, and a larger protein, including the CHR and MPER regions, suggest that the interaction of C8 with the MPER region, the origin of the antiviral activity of C8, is disfavored in the presence of gp36 NHR in the simulation. This evidence can be useful for interpreting the molecular mechanism that leads to interference with the activity of C8, providing information on the folding/unfolding mechanism of the viral glycoprotein to design new strategies to inhibit viral entry.
猫免疫缺陷病毒（FIV）与人类免疫缺陷病毒（HIV）具有结构相似性：表面糖蛋白 gp36 对应于 HIV 的 gp41，后者驱动病毒-宿主细胞相互作用，并被肽进入抑制剂恩夫韦肽靶向。基于开发抗 FIV 治疗的类似药物设计策略，本研究调查了 gp36 NHR，这是源自 gp36 的一个区域的肽序列，该区域先前被发现干扰肽 C8 的抗病毒活性，而 C8 则源自 gp36 的 MPER。CD、NMR 和 MD 模拟用于探测 gp36 NHR 在 SDS 胶束模拟膜环境中的构象特征。我们的数据表明，gp36 NHR 的特征是三个动态螺旋结构。涉及 gp36 NHR、C8 和更大蛋白（包括 CHR 和 MPER 区域）的 MD 模拟表明，在模拟中存在 gp36 NHR 的情况下，C8 与 MPER 区域的相互作用（C8 抗病毒活性的起源）是不利的。这一证据可用于解释导致 C8 活性干扰的分子机制，为设计抑制病毒进入的新策略提供有关病毒糖蛋白折叠/展开机制的信息。
