Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
Institute of Virology, Philipps University of Marburg, 35043 Marburg, Germany; German Centre for Infection Research (DZIF), Partner Site Gießen-Marburg-Langen, 35043 Marburg, Germany.
Antiviral Res. 2018 Apr;152:26-35. doi: 10.1016/j.antiviral.2018.02.003. Epub 2018 Feb 8.
Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule has previously been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent.
埃博拉病毒（EBOV）和寨卡病毒（ZIKV）是最近全球卫生威胁的罪魁祸首。由于目前尚无针对这两种新出现病原体的预防疫苗或抗病毒药物，我们评估了分子镊子 CLR01 是否可以抑制 EBOV 和 ZIKV 感染。这种小分子先前已被证明通过与病毒包膜中富含脂筏的区域选择性相互作用来灭活 HIV-1 和疱疹病毒，从而导致膜破坏和丧失感染性。我们发现 CLR01 确实可以以剂量依赖性方式阻止 EBOV 和 ZIKV 的感染。该镊子抑制了源自生殖道和中枢神经系统的流行 ZIKV 株的感染，并且在存在精液、唾液、尿液和脑脊液的情况下仍具有抗病毒活性。我们的研究结果表明，CLR01 是一种广谱包膜病毒抑制剂，具有作为预防性杀菌剂或抗病毒剂的前景。
