小分子抗马脑炎病毒药物的研究进展。
Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.
机构信息
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.
出版信息
Viruses. 2023 Feb 1;15(2):413. doi: 10.3390/v15020413.
Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV, respectively) are arboviruses that are highly pathogenic to equines and cause significant harm to infected humans. Currently, human alphavirus infection and the resulting diseases caused by them are unmitigated due to the absence of approved vaccines or therapeutics for general use. These circumstances, combined with the unpredictability of outbreaks-as exemplified by a 2019 EEE surge in the United States that claimed 19 patient lives-emphasize the risks posed by these viruses, especially for aerosolized VEEV and EEEV which are potential biothreats. Herein, small molecule inhibitors of VEEV, WEEV, and EEEV are reviewed that have been identified or advanced in the last five years since a comprehensive review was last performed. We organize structures according to host- versus virus-targeted mechanisms, highlight cellular and animal data that are milestones in the development pipeline, and provide a perspective on key considerations for the progression of compounds at early and later stages of advancement.
委内瑞拉、西部和东部马脑炎阿尔法病毒(分别为 VEEV、WEEV 和 EEEV)是虫媒病毒,对马具有高度致病性,并导致感染人类的严重疾病。目前,由于没有批准的疫苗或一般用途的治疗方法,人类感染阿尔法病毒以及由此产生的疾病仍然无法得到控制。这些情况,再加上疫情的不可预测性——例如 2019 年美国爆发的 EEE,导致 19 名患者死亡——突显了这些病毒带来的风险,特别是对于可能构成生物威胁的气溶胶化的 VEEV 和 EEEV。在此,综述了过去五年中发现或进展的 VEEV、WEEV 和 EEEV 的小分子抑制剂。我们根据宿主与病毒靶向机制对结构进行组织,突出了在开发管道中具有里程碑意义的细胞和动物数据,并就化合物在早期和后期阶段的进展提供了关键考虑因素的观点。