Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7028 Trondheim, Norway.
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
Viruses. 2021 Sep 4;13(9):1768. doi: 10.3390/v13091768.
SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNα and that both Serpin E1 and nafamostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.
由于缺乏有效、快速部署和广泛可用的治疗方法，SARS-CoV-2 及其疫苗/免疫逃逸变体继续对公共健康构成严重威胁。在这里，我们通过结合 Pegasys（IFNα）和那法莫司他来有效地抑制细胞培养和仓鼠中的 SARS-CoV-2 感染，从而应对这些挑战。我们的结果表明，丝氨酸蛋白酶抑制剂 E1 是 IFNα 抗病毒活性的重要介质，丝氨酸蛋白酶抑制剂 E1 和那法莫司他都可以靶向同一细胞因子 TMPRSS2，该因子在病毒复制中起关键作用。药物的低剂量联合使用可能具有几个临床优势，包括较少的不良反应和改善患者的预后。因此，我们的研究可能为持续的大流行和潜在的未来冠状病毒爆发提供了一个积极的解决方案，这在世界许多地方仍然是迫切需要的。
