García C C, Candurra N A, Damonte E B
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Antivir Chem Chemother. 2000 May;11(3):231-7. doi: 10.1177/095632020001100306.
Fifteen antiretroviral Zn-finger active compounds with diverse chemical structures, including azoic compounds, hydrazide derivatives, disulphide-based reagents and others were screened in vitro against Junin virus (JUNV), the aetiological agent of Argentine haemorrhagic fever, by a virus yield inhibition assay in Vero cells. Cytotoxicity was evaluated simultaneously by the MTT method. Of the compounds, three were totally inactive as antivirals, nine presented moderate anti JUNV-activity and three were truly active with EC50 (effective concentration 50%) values in the range 6.5-9.3 microM and with selectivity indices greater than 10. The most active inhibitors, named NSC20625, 3-7 and 2-71, demonstrated a broad range of action against arenaviruses, including several attenuated and pathogenic strains of JUNV as well as the antigenically related Tacaribe virus (TACV) and Pichinde virus (PICV). The direct treatment of JUNV and TACV virions with the compounds showed two types of behaviour: the aromatic disulphide NSC20625 was a very potent virucidal agent, whereas the other two compounds exhibited moderate or negligible virus-inactivating properties.
通过在Vero细胞中进行病毒产量抑制试验，对15种具有不同化学结构的抗逆转录病毒锌指活性化合物进行了体外筛选，这些化合物包括偶氮化合物、酰肼衍生物、二硫化物基试剂等，以检测其对阿根廷出血热病原体胡宁病毒（JUNV）的作用。同时采用MTT法评估细胞毒性。在这些化合物中，有3种作为抗病毒药物完全无活性，9种表现出中度抗JUNV活性，3种真正具有活性，其半数有效浓度（EC50）值在6.5-9.3微摩尔范围内，选择性指数大于10。活性最高的抑制剂，命名为NSC20625、3-7和2-71，对沙粒病毒表现出广泛的作用范围，包括几种减毒和致病的JUNV毒株以及抗原相关的塔卡里贝病毒（TACV）和皮钦德病毒（PICV）。用这些化合物直接处理JUNV和TACV病毒粒子表现出两种行为：芳香族二硫化物NSC20625是一种非常有效的杀病毒剂，而其他两种化合物表现出中度或可忽略不计的病毒灭活特性。
