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首页> 外文期刊>Antiviral chemistry & chemotherapy >Maporal virus as a surrogate for pathogenic New World hantaviruses and its inhibition by favipiravir.
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Maporal virus as a surrogate for pathogenic New World hantaviruses and its inhibition by favipiravir.

机译：Maporal病毒是新世界致病性汉坦病毒的替代品，并被favipiravir抑制。

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BACKGROUND: Pathogenic hantaviruses geographically distributed in the Old World cause haemorrhagic fever with renal syndrome (HFRS), whereas New World hantaviruses are the aetiological agents of hantavirus cardiopulmonary syndrome (HCPS). Ribavirin, a drug associated with toxicities, is presently indicated for treatment of HFRS, whereas treatment of the more frequently lethal HCPS is limited to supportive care. Because of the need for safe and effective antivirals to treat severe hantaviral infections, we evaluated favipiravir (T-705) against Dobrava and Maporal viruses as representative Old World and New World hantaviruses, respectively. Dobrava virus causes HFRS in Europe. Maporal virus (MPRLV), recently isolated from western Venezuela, is phylogenetically similar to Andes virus, the principal cause of HCPS in Argentina. METHODS: Hantavirus replication in the presence of various inhibitors was measured by focus-forming unit assays and quantitative reverse transcriptase PCR. Phylogenetic relationships were assessed by the neighbour-joining and bootstrap consensus methods. RESULTS: Here, we show that infection of Vero E6 cells with MPRLV is dependent on beta3 integrins, similar to that reported for pathogenic hantaviruses. Furthermore, by analysis of molecular determinants associated with the G1 glycoprotein cytoplasmic tail, we show the close genetic proximity of MPRLV to other HCPS-causing hantaviruses in these regions predictive of pathogenicity. We also demonstrate anti-hantavirus activity by favipiravir with inhibitory concentrations ranging from 65 to 93 muM and selectivity indices >50. CONCLUSIONS: Our data suggest that MPRLV may serve as a safer alternative to modelling infection caused by the highly lethal Andes virus and that hantaviruses are sensitive to the effects of favipiravir in cell culture.
机译：背景：地理分布在旧大陆的致病性汉坦病毒引起肾综合征（HFRS）出血热，而新大陆的汉坦病毒是汉坦病毒性心肺综合征（HCPS）的病原体。利巴韦林是一种与毒性有关的药物，目前被认为可用于治疗HFRS，而更致命的HCPS的治疗仅限于支持治疗。由于需要安全有效的抗病毒药物来治疗严重的汉坦病毒感染，因此我们评估了针对Dobrava和Maporal病毒的favipiravir（T-705）分别代表旧世界和新世界汉坦病毒。 Dobrava病毒在欧洲引起HFRS。最近从委内瑞拉西部分离出的Maporal病毒（MPRLV）在系统发育上类似于安第斯病毒，后者是阿根廷HCPS的主要原因。方法：通过聚焦形成单位测定和定量逆转录酶PCR来测量在各种抑制剂存在下的汉坦病毒复制。系统发育关系通过邻居加入和自举共识方法进行评估。结果：在这里，我们显示MPRLV对Vero E6细胞的感染依赖于beta3整合素，类似于致病性汉坦病毒的报道。此外，通过分析与G1糖蛋白胞质尾相关的分子决定簇，我们显示了在这些区域中MPRLV与其他引起HCPS的汉坦病毒的遗传接近性，可预测致病性。我们还证明了favipiravir的抗汉坦病毒活性具有抑制浓度，范围从65到93μM，选择性指数> 50。结论：我们的数据表明，MPRLV可以作为模拟由高致死性安第斯病毒引起的感染的更安全替代方法，汉坦病毒对favipiravir在细胞培养中的作用敏感。

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