Nuclear Signaling Lab., Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Monash, Victoria 3800, Australia.
Cancer Targeting and Nuclear Therapeutics Lab., Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Monash, Victoria 3800, Australia.
Cells. 2020 Sep 15;9(9):2100. doi: 10.3390/cells9092100.
The small molecule macrocyclic lactone ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its apparent exciting potential as an antiviral. It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. Excitingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Phase III human clinical trials have been completed for DENV, with >50 trials currently in progress worldwide for SARS-CoV-2. This mini-review discusses the case for ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.
小分子大环内酯类伊维菌素，经美国食品和药物管理局批准用于寄生虫感染，由于其作为抗病毒药物的明显兴奋潜力，在过去八年中受到了新的关注。它在高通量化学筛选中被鉴定为抑制宿主异二聚体导入蛋白（IMP）α/β1 复合物识别核定位的人类免疫缺陷病毒 1（HIV-1）整合酶蛋白，并且此后已被证明直接结合 IMPα 以诱导构象变化，从而阻止其在介导关键病毒和宿主蛋白的核输入中的正常功能。令人兴奋的是，细胞培养实验显示出对 HIV-1、登革热病毒（DENV）、寨卡病毒、西尼罗河病毒、委内瑞拉马脑炎病毒、基孔肯雅热病毒、伪狂犬病病毒、腺病毒和严重急性呼吸系统综合征冠状病毒 2（COVID-19）的强大抗病毒作用。登革热病毒的 III 期人体临床试验已经完成，目前全球有超过 50 项针对 SARS-CoV-2 的试验正在进行中。这篇迷你评论讨论了伊维菌素作为一种针对包括 SARS-CoV-2 在内的多种病毒的宿主定向广谱抗病毒药物的情况。
