Identification of active antiviral compounds against a New York isolate of West Nile virus
Identification of active antiviral compounds against a New York isolate of West Nile virus
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DOI：
10.1016/s0166-3542(02)00013-x
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发表时间：
2002-07-01
影响因子：
7.6
通讯作者：
Tseng, C
中科院分区：
文献类型：
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作者：
Morrey, JD;Smee, DF;Tseng, C
最近在美国爆发的西尼罗河病毒（WNV）增加了对这种疾病的有效治疗方法的需求。化疗方法可能是一种合理的策略，因为病毒感染通常不是慢性的，抗病毒药物已被确定在体外对其他黄病毒有效。在Vero细胞中测试了34种物质对最近在纽约分离的西尼罗河病毒的感染作用，并在MA-104细胞中评估了活性化合物。其中一些化合物还在Vero细胞中对1937年乌干达分离的西尼罗河病毒进行了评估。有6种化合物对病毒诱导的CPE有效，其50%有效浓度（EC50）小于10马克/毫升，选择性指数（SI）大于10。已知的与GTP、UTP和TTP合成有关的欧罗替丁单磷酸脱羧酶和肌苷单磷酸脱氢酶抑制剂是最有效的。其中，6-脲嘧啶、6-三乙酸脲嘧啶、环戊基leytosine （cfe - c）、霉酚酸和吡唑呋喃对纽约分离物的活性最强，其次为2-硫代-6-脲嘧啶。在初始感染Vero细胞2天后，通过病毒产率降低实验证实了6-氮脲的抗西尼罗河病毒活性。利巴韦林的中性红色试验平均EC50仅为106马克/毫升，对纽约分离株的平均SI为9.4，对乌干达分离株的效果仅略高。纽约和乌干达分离株的药物敏感性存在一些差异，但根据其作用方式对药物进行分类进行比较时，发现两株之间的活性相似之处。(C) 2002 Elsevier Science B.V.版权所有
The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies for this disease. A chemotherapeutic approach may be a reasonable strategy because the virus infection is typically not chronic and antiviral drugs have been identified to be effective in vitro against other flaviviruses. A panel of 34 substances was tested against infection of a recent New York isolate of WNV in Vero cells and active compounds were also evaluated in MA-104 cells. Some of these compounds were also evaluated in Vero cells against the 1937 Uganda isolate of the WNV. Six compounds were identified to be effective against virus-induced CPE with 50% effective concentrations (EC50) less than 10 mug/ml and with a selectivity index (SI) of greater than 10. Known inhibitors of orotidine monophosphate decarboxylase and inosine monophosphate dehydrogenase involved in the synthesis of GTP, UTP, and TTP were most effective. The compounds 6-azauridine, 6-azauridine triacetate, cyclopententyleytosine (CPE-C), mycophenolic acid and pyrazofurin appeared to have the greatest activities against the New York isolate, followed by 2-thio-6-azauridine. Anti-WNV activity of 6-azauridine was confirmed by virus yield reduction assay when the assay was performed 2 days after initial infection in Vero cells. The neutral red assay mean EC50 of ribavirin was only 106 mug/ml with a mean SI of 9.4 against the New York isolate and only slightly more effective against the Uganda isolate. There were some differences in the drug sensitivities of the New York and Uganda isolates, but when comparisons were made by categorizing drugs according to their modes of action, similarities of activities between the two isolates were identified. (C) 2002 Elsevier Science B.V. All rights reserved.