El-Bitar Alaa M H, Sarhan Moustafa M H, Aoki Chie, Takahara Yusuke, Komoto Mari, Deng Lin, Moustafa Mohsen A, Hotta Hak
Department of Zoology, Faculty of Science, Al-Azhar University, Assiut, Egypt.
Division of Microbiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, , Hyogo, Japan.
Virol J. 2015 Mar 24;12:47. doi: 10.1186/s12985-015-0276-6.
Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions.
The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities.
S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV.
S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.
丙型肝炎病毒(HCV)是一个重大的全球健康问题,可导致慢性肝炎、肝硬化和肝细胞癌。目前仍亟需开发出耐受性良好、治愈率高且副作用少的治疗方案。近年来,天然抗菌肽(AMPs)作为生物化合物受到了更多关注,并且可以作为开发治疗药物(包括针对多种病毒的抗病毒药物)的良好模板。已经从包括蝎子在内的不同有毒动物的毒液中鉴定出了各种抗菌肽。
使用Huh7.5细胞和HCV的J6/JFH1-P47毒株,通过细胞培养方法评估了从五种埃及蝎子(金蝎、东方金蝎、澳链尾蝎、双色链尾蝎和摩洛哥杀牛蝎)获得的粗毒液的潜在抗病毒活性。进行了添加时间实验和毒液酶活性的失活实验,以确定抗HCV活性的特征。
摩洛哥杀牛蝎和澳链尾蝎的毒液表现出抗HCV活性,50%抑制浓度(IC₅₀)分别为6.3±1.6和88.3±5.8μg/ml。摩洛哥杀牛蝎毒液(30μg/ml)通过杀病毒作用损害了培养基中的HCV感染性,但对细胞内的HCV没有影响。该毒液的抗HCV活性不受金属蛋白酶抑制剂或60°C加热的抑制。抗病毒活性优先针对HCV。
摩洛哥杀牛蝎毒液被认为是用于鉴定和开发针对病毒进入步骤的新型抗HCV药物的良好天然来源。据我们所知,这是第一份描述埃及蝎子毒液对HCV抗病毒活性的报告,可能会开辟一条发现源自蝎子毒液的抗病毒化合物的新途径。