State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Peptides. 2011 Jan;32(1):11-9. doi: 10.1016/j.peptides.2010.10.008. Epub 2010 Oct 13.
Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. There is no vaccine available for HCV, and almost half of patients cannot be cured using standard combination therapy. Thus, new anti-HCV strategies and drugs are urgently needed. Here, the gene encoding a new α-helical peptide, Hp1090, was screened from the venomous gland cDNA library of the scorpion Heterometrus petersii. Structural analysis showed that Hp1090 is an amphipathic α-helical peptide. In vitro HCV RNA inhibitory assays indicated that Hp1090 peptide inhibited HCV infection with an IC(50) of 7.62 μg/ml (5.0 μM), whereas Hp1035 peptide, showing high homology to Hp1090, exhibited no anti-HCV activity. Hp1090 acted as a viricide against HCV particles in vitro and prevented the initiation of HCV infection. Furthermore, this peptide interacted with HCV particles directly and rapidly permeabilized phospholipid membranes. Collectively, it seems that Hp1090 is virocidal for HCV in vitro, directly interacting with the viral membrane and decreasing the virus infectivity. These results suggest that Hp1090 could be considered an anti-HCV lead compound with virocidal mechanism that offers a potential therapeutic approach to HCV infection. Our work opens a new avenue for antiviral drug discovery in natural scorpion venom.
丙型肝炎病毒（HCV）是慢性肝病、肝硬化和肝细胞癌的主要病因。目前尚无 HCV 疫苗，几乎一半的患者不能通过标准联合疗法治愈。因此，急需新的抗 HCV 策略和药物。本研究从蝎子 Heterometrus petersii 的毒腺 cDNA 文库中筛选到一个新的α-螺旋肽基因，命名为 Hp1090。结构分析表明 Hp1090 是一种两亲性α-螺旋肽。体外 HCV RNA 抑制试验表明，Hp1090 肽以 7.62 μg/ml（5.0 μM）的 IC50 抑制 HCV 感染，而与 Hp1090 具有高度同源性的 Hp1035 肽则没有抗 HCV 活性。Hp1090 在体外对 HCV 颗粒具有杀病毒作用，并能阻止 HCV 感染的起始。此外，该肽能与 HCV 颗粒直接相互作用并迅速破坏磷脂膜。综上所述，Hp1090 似乎在体外对 HCV 具有杀病毒作用，直接与病毒膜相互作用，降低病毒感染力。这些结果表明，Hp1090 可作为一种具有杀病毒机制的抗 HCV 先导化合物，为 HCV 感染提供了一种潜在的治疗方法。我们的工作为从天然蝎毒液中发现抗病毒药物开辟了新途径。
