Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI)(2), Nonthaburi, Thailand.
Virology. 2010 Sep 15;405(1):157-64. doi: 10.1016/j.virol.2010.06.012. Epub 2010 Jul 2.
Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants.
两个位于人类免疫缺陷病毒 1 型（HIV-1）包膜糖蛋白 gp41 中的α-螺旋七肽重复序列，N-HR 和 C-HR，通过形成 6 螺旋束在膜融合中发挥重要作用。C34 是一种模拟 C-HR 的肽，可抑制 6 螺旋束的形成；因此，它有可能成为一种新型抗逆转录病毒化合物。为了提高 C34 抑制 HIV-1 复制的效果，我们基于对 6 螺旋束稳定构象的计算分析，设计了基于 C34 的新型肽。新设计的肽对含有 CRF01_AE、B 亚型或 C 亚型Env 的重组病毒的复制具有比 C34 或融合抑制剂 T-20 更强的抑制作用。此外，这些肽抑制了 T-20 耐药病毒的复制。我们提出，这些肽可用于开发新型抗逆转录病毒化合物，以抑制各种 HIV-1 亚型以及 T-20 耐药变异体的复制。
