Background

Recent recognition of invasive astrovirus infections, including encephalitis and viremia in humans, have highlighted the need for effective anti-astrovirus therapeutics. However, there is a paucity of data regarding the in vitro activity of broad-spectrum RNA antivirals against astroviruses, including ribavirin and favipiravir.

Objectives

We quantified the EC50 values for ribavirin and favipiravir against two human astrovirus strains, astrovirus VA1 (VA1) and human astrovirus 4 (HAstV4).

Study Design

Caco-2 cells were infected with VA1 or HAstV4 in the presence of ribavirin or favipiravir (dose range 0.1-1000 μM), and the cells were maintained in media containing the drugs for 72 hours. Viral RNA was extracted and quantified by qRT-PCR. As a surrogate for cytotoxicity, cellular adenosine triphosphate (ATP) from each drug treatment was also measured.

Results

VA1 replication was inhibited 10-100-fold by both ribavirin (EC50 = 154μM) and favipiravir (EC50 = 246 μM). In contrast, ribavirin inhibited HAstV4 replication (EC50 = 268 μM) but favipiravir only reduced replication by 44% at the highest dose. Mild reductions in ATP (17-31%) was only observed at the highest concentration of ribavirin (1000 μM) and no significant decrease in ATP was detected for any concentration of favipiravir.

Conclusions

Ribavirin inhibited both human astrovirus species and favipiravir was only active against VA1. In the future, the in vivo efficacy of these drugs could be tested with development of an animal model of human astrovirus infection

中文翻译：

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病毒唑和法维吡韦对人星状病毒的抗病毒活性。

背景

最近对侵入性星状病毒感染（包括人类脑炎和病毒血症）的认识突出了对有效抗星状病毒治疗剂的需求。但是，关于广谱RNA抗病毒剂抗星状病毒（包括利巴韦林和favipiravir）的体外活性的数据很少。

目标

我们针对两种人类星状病毒株，星状病毒VA1（VA1）和人类星状病毒4（HAstV4）量化了利巴韦林和favipiravir的EC50值。

学习规划

在存在病毒唑或法维拉韦（剂量范围为0.1-1000μM）的情况下，用VA1或HAstV4感染Caco-2细胞，并将细胞在含有药物的培养基中保存72小时。提取病毒RNA并通过qRT-PCR定量。作为细胞毒性的替代物，还测量了每种药物治疗产生的细胞三磷酸腺苷（ATP）。

结果

病毒唑（EC50 =154μM）和依维拉韦（EC50 = 246μM）抑制VA1复制10-100倍。相比之下，利巴韦林抑制HAstV4复制（EC50 = 268μM），但在最高剂量下，favipiravir仅使复制减少44％。仅在最高浓度的利巴韦林（1000μM）下观察到ATP的轻度降低（17-31％），而对于任何浓度的依维拉韦，ATP均未检测到显着降低。

结论

利巴韦林同时抑制人类星状病毒，而favipiravir仅对VA1有效。将来，可以通过开发人类星状病毒感染的动物模型来测试这些药物的体内功效。