Filociclovir is a potent inhibitor of human adenovirus F41.
Filociclovir is a potent inhibitor of human adenovirus F41.
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DOI：
10.1016/j.antiviral.2022.105431
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发表时间：
2022-10
影响因子：
7.6
通讯作者：
A. Tollefson;I. Hussein;K. Toth;T. Bowlin
中科院分区：
文献类型：
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作者：
A. Tollefson;I. Hussein;K. Toth;T. Bowlin
全球已经报告了以前健康的儿童中出现的急性非戊型肝炎病例群。在35个国家至少发现了1010个病例，其中5%的病例需要肝移植，2%的病例死亡。确切的原因尚不清楚，但有间接证据表明，人腺病毒F41(HAdV-F41)可能在其中发挥作用。目前还没有抗病毒药物被批准用于治疗人腺病毒感染。此外，众所周知，HAdV-F41很难在细胞培养中生长，这阻碍了研究一种抗病毒化合物对这种病毒的疗效。在这里，我们通过两种方法，即感染细胞的免疫染色和病毒产量减少试验，证明了核苷类似物非诺昔洛韦(FCV)是HAdV-F41的有效抑制物。将FCV的活性与其他3种已知的抗病毒药物：西多福韦(CDV)、更昔洛韦(GCV)和伐更昔洛韦(VGCV)进行了比较。在本研究考察的4种化合物中，FCV的效力最强，EC50值为3.5%μM。这些化合物按效力排序如下：FCV、CDV、≥和vGCV。此外，在病毒产量减少试验中，FCV的效力是CDV的10倍。这份报告为研究界测试HAdV-F41的抗病毒药物提供了及时和有价值的方法。我们的发现也支持了FCV在包括儿科肝炎在内的各种治疗应用中的持续开发，如果在未来确定因果关系的话。
Clusters of acute non HepA-E hepatitis cases in previously healthy children have been reported globally. At least, 1010 cases were identified in 35 countries, 5% of those cases required liver transplantation and 2% died. The exact cause is not yet known, but there is circumstantial evidence suggesting that human adenovirus F41 (HAdV-F41) might be playing a role. No antiviral drug has been approved for treating human adenovirus infections. Furthermore, HAdV-F41 is notoriously difficult to grow in cell culture, which hindered studying the efficacy of an antiviral compound against this virus. Here, we show that filociclovir (FCV), a nucleoside analog, is a potent inhibitor of HAdV-F41 in cell culture using 2 approaches, namely immunostaining of infected cells and virus yield reduction assay. The activity of FCV was compared to 3 other known antivirals: cidofovir (CDV), ganciclovir (GCV) and valganciclovir (VGCV). Among the 4 compounds examined in this study, FCV was the most potent, with an EC50of 3.5 μM. These compounds can be ranked by potency as follows: FCV > CDV > GCV ≥ VGCV. In addition, FCV was 10-fold more potent than CDV in a virus yield reduction assay. This report provides timely and valuable methodologies to the research community for testing antivirals against HAdV-F41. Our findings also support the continued development of FCV for various therapeutic applications, including pediatric hepatitis, if a causal relationship is firmly established in the future.