Diani Erica, Lagni Anna, Lotti Virginia, Tonon Emil, Cecchetto Riccardo, Gibellini Davide
Department of Diagnostic and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy.
Unit of Microbiology, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy.
Microorganisms. 2023 Sep 28;11(10):2427. doi: 10.3390/microorganisms11102427.
Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality-about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to and experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.
黄病毒可导致人类出现广泛临床谱中的多种病理状况，具有潜在的严重临床表现，包括出血性和神经紊乱。在人类黄病毒中，一些病毒蛋白具有高度保守性，是药物设计靶点的良好候选对象。从流行病学角度来看，黄病毒每年在全球导致超过4亿例感染病例。特别是黄热病、登革热、西尼罗河病毒和寨卡病毒，其发病率和死亡率都很高——每年估计约有2万例死亡。由于它们依赖人类媒介，近年来，由于气候和社会条件的变化，它们的地理分布范围有所扩大。尽管有这些流行病学和临床方面的情况，但针对这些感染的抗病毒治疗方法有限。在本综述中，我们描述了目前正在评估用于治疗黄病毒感染的主要化合物以及临床试验中面临的挑战，概述了它们的作用机制，以便对正在进行的研究进行综述。根据我们的综述，缺乏针对黄病毒的获批抗病毒药物导致了旨在鉴定能够干扰一个或多个病毒周期步骤的化合物的实验。然而，目前尚无获批的抗病毒药物仍然构成了一个重大的公共卫生问题。
