Hotard Anne L, He Biao, Nichol Stuart T, Spiropoulou Christina F, Lo Michael K
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Antiviral Res. 2017 Aug;144:147-152. doi: 10.1016/j.antiviral.2017.06.011. Epub 2017 Jun 17.
The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4'-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae. We observed similar levels of R1479 antiviral activity across the family, regardless of virus genus. Our brief study expands the documented range of viruses susceptible to R1479, and provides the basis for future investigation and development of 4'-modified nucleoside analogs as potential broad-spectrum antiviral therapeutics across both positive and negative-sense RNA virus families.
尼帕病毒和亨德拉病毒这两种亨尼帕病毒是高致病性人畜共患副粘病毒，已在人类中引发致命的脑炎和呼吸道疾病疫情。尽管已有一种获许可的马用亨德拉病毒疫苗，且有一种中和单克隆抗体在非人类灵长类动物中显示出对亨尼帕病毒感染有效，但仍没有获批的供人类使用的治疗方法或疫苗。为探索开发针对亨尼帕病毒的小分子核苷抑制剂的可能性，我们评估了4'-叠氮胞苷（R1479，一种先前确定可抑制黄病毒的药物）对亨尼帕病毒以及副粘病毒科其他代表性成员的抗病毒活性。我们观察到，无论病毒属如何，整个科中R1479的抗病毒活性水平相似。我们的简短研究扩展了已记录的对R1479敏感的病毒范围，并为未来研究和开发4'-修饰核苷类似物作为正链和负链RNA病毒科潜在的广谱抗病毒治疗药物提供了基础。
