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利巴韦林(T-705)对腮腺炎病毒复制的体外抑制作用。

In vitro inhibition of mumps virus replication by favipiravir (T-705).

机构信息

Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

出版信息

Antiviral Res. 2020 Aug;180:104849. doi: 10.1016/j.antiviral.2020.104849. Epub 2020 Jun 14.

Abstract

During the last decade multiple mumps outbreaks have occurred in the U.S. despite high two dose MMR coverage with most cases detected among two dose MMR vaccine recipients. Waning immunity, the evolution of wild-type virus strains, and settings with intense exposure have contributed to the resurgence of mumps. Typically, mumps virus infections resolve without serious clinical sequelae; however, serious complications may occur among unvaccinated or severely immunocompromised individuals. Favipiravir (T-705) has been shown to have in vitro anti-viral activity against a broad range of positive and negative strand RNA viruses. Here, we demonstrate that T-705 inhibits the growth of wildtype and vaccine strains of mumps virus in vitro at low micro-molar concentrations (EC 8-10μM). We did not observe the development of resistance after five subsequent passages at low concentrations of drug. Both viral RNA and protein synthesis were selectively reduced compared to host mRNA and protein synthesis. Antiviral treatment options for mumps virus infection may be valuable, especially for areas with a high disease burden or for cases with severe complications. These results presented here suggest that further studies are warranted.

摘要

在过去的十年中,尽管美国的两剂次麻疹、腮腺炎、风疹(MMR)疫苗覆盖率很高,但仍多次出现腮腺炎暴发疫情,大多数病例发生在两剂次 MMR 疫苗接种者中。免疫衰减、野生型病毒株的演变以及暴露强度大的环境促成了腮腺炎的再次流行。通常情况下,腮腺炎病毒感染可自行消退而不遗留严重的临床后遗症;然而,未接种疫苗或严重免疫功能低下的个体可能会出现严重并发症。法匹拉韦(T-705)已被证明具有针对广泛的正链和负链 RNA 病毒的体外抗病毒活性。在这里,我们证明 T-705 在低微摩尔浓度(EC8-10μM)下可抑制野生型和疫苗株腮腺炎病毒的体外生长。在低药物浓度下连续传代 5 次后,我们没有观察到耐药性的发展。与宿主 mRNA 和蛋白质合成相比,病毒 RNA 和蛋白质的合成均被选择性地降低。针对腮腺炎病毒感染的抗病毒治疗选择可能具有重要价值,尤其是在疾病负担较高的地区或出现严重并发症的病例中。这里提出的结果表明,进一步的研究是必要的。

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