FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.

FDA批准了寄生虫适应症，小分子伊维菌素由于其作为抗病毒药的潜力在过去8年中一直受到越来越多的关注。我们首先在高通量化合物库筛选中鉴定了伊维菌素作为一种有效抑制宿主导入素（IMP）α/β1异二聚体识别核定位人类免疫缺陷病毒-1（HIV-1）整合酶蛋白的药物，并最近进行了验证它具有直接与IMPα结合从而引起构象变化的能力，从而阻止了它在关键病毒以及宿主蛋白的核输入中的作用。细胞培养实验表明，它对包括HIV-1，登革热，寨卡病毒和西尼罗河病毒，委内瑞拉马脑炎病毒，基孔肯雅热，伪狂犬病病毒，腺病毒和SARS-CoV-2（COVID-19）在内的各种病毒具有强大的抗病毒作用）。目前，针对SARS-CoV-2的全球近70个临床试验正在进行中。尽管这些研究很少完成，但是可获得的结果以及观察/回顾性研究的结果均表明了临床获益。在这里，我们讨论了伊维菌素作为宿主导向的广谱抗病毒药物（包括SARS-CoV-2）的案例。