A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles.
A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles.
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蝎毒肽 Ev37 通过碱化酸性细胞器来限制病毒后期进入
DOI：
10.1074/jbc.ra118.005015
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发表时间：
2019-01-04
期刊：
影响因子：
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通讯作者：
Cao Z
中科院分区：
文献类型：
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作者：
Li F;Lang Y;Ji Z;Xia Z;Han Y;Cheng Y;Liu G;Sun F;Zhao Y;Gao M;Chen Z;Wu Y;Li W;Cao Z
病毒感染仍然威胁着全世界的人类健康，每年都有许多人死于病毒性疾病。然而，没有有效的疫苗或药物来预防或管理大多数病毒性疾病。因此，广谱抗病毒药物的发现和开发仍是当务之急。在这里，我们表达和纯化的毒液肽，Ev37，从蝎子Euscorpiops validus在原核系统中。我们发现rEv 37可以在非细胞毒性浓度下以剂量依赖性方式抑制登革病毒2型（DENV-2）、丙型肝炎病毒（HCV）、寨卡病毒（ZIKV）和单纯疱疹病毒1型（HSV-1）感染，但在体外对仙台病毒（SeV）和腺病毒（AdV）感染没有影响。此外，rEv 37碱化酸性细胞器以防止病毒膜-内体膜的低pH依赖性融合，其主要阻断病毒基因组从内体释放到细胞质，然后限制病毒晚期进入。两者合计，我们的研究结果表明，蝎毒肽Ev37是一种广谱抗病毒剂，具有特定的分子机制，针对病毒在进入宿主细胞过程中经历低pH依赖性融合激活。我们的结论是，Ev37是一个潜在的候选开发作为一种抗病毒药物。
Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH–dependent fusion of the viral membrane–endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH–dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.