Pasquato Antonella, Kunz Stefan
a Institute of Microbiology , University Hospital Center and University of Lausanne , Lausanne , Switzerland.
Expert Opin Drug Discov. 2016;11(4):383-93. doi: 10.1517/17460441.2016.1153626. Epub 2016 Mar 7.
Arenaviruses are enveloped negative stranded viruses endemic in Africa, Europe and the Americas. Several arenaviruses cause severe viral hemorrhagic fever with high mortality in humans and pose serious public health threats. So far, there are no FDA-approved vaccines and therapeutic options are restricted to the off-label use of ribavirin. The major human pathogenic arenaviruses are classified as Category A agents and require biosafety level (BSL)-4 containment.
Herein, the authors cover the recent progress in the development of BSL2 surrogate systems that recapitulate the entire or specific steps of the arenavirus life cycle and are serving as powerful platforms for drug discovery. Furthermore, they highlight the identification of selected novel drugs that target individual steps of arenavirus multiplication describing their discovery, their targets, and mode of action.
The lack of effective drugs against arenaviruses is an unmatched challenge in current medical virology. Novel technologies have provided important insights into the basic biology of arenaviruses and the mechanisms underlying virus-host cell interaction. Significant progress of our understanding of how the virus invades the host cell paved the way to develop powerful novel screening platforms. Recent efforts have provided a range of promising drug candidates currently under evaluation for therapeutic intervention in vivo.
沙粒病毒是包膜负链病毒,在非洲、欧洲和美洲流行。几种沙粒病毒可导致人类严重病毒性出血热,死亡率很高,对公共卫生构成严重威胁。到目前为止,尚无美国食品药品监督管理局(FDA)批准的疫苗,治疗选择仅限于利巴韦林的非标签使用。主要的人类致病性沙粒病毒被归类为A类病原体,需要在生物安全4级(BSL-4)条件下进行操作。
在此,作者介绍了BSL2替代系统开发的最新进展,该系统概括了沙粒病毒生命周期的全部或特定步骤,是药物发现的强大平台。此外,他们强调了针对沙粒病毒增殖各个步骤的选定新型药物的鉴定,描述了它们的发现、靶点和作用方式。
缺乏针对沙粒病毒的有效药物是当前医学病毒学中一项无与伦比的挑战。新技术为沙粒病毒的基础生物学以及病毒与宿主细胞相互作用的机制提供了重要见解。我们对病毒如何侵入宿主细胞的理解取得了重大进展,为开发强大的新型筛选平台铺平了道路。最近的努力提供了一系列有前景的候选药物,目前正在评估其在体内的治疗干预效果。