Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, 28159, Chungcheongbuk-do, Republic of Korea.
Division of Infectious Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University, Seoul, Republic of Korea.
Sci Rep. 2020 Oct 1;10(1):16200. doi: 10.1038/s41598-020-72879-7.
The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 10-, 10- and 10-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
目前，由于缺乏有效的治疗药物，冠状病毒（COVID-19）大流行愈演愈烈。值得注意的是，患有 COVID-19 且合并高血压和心脏病等合并症的患者死亡率更高。应对这一问题的有效策略是重新利用具有抗病毒活性的药物来发挥治疗作用。地高辛（DIG）和哇巴因（OUA）是美国食品和药物管理局（FDA）批准用于心脏病的药物，对多种冠状病毒具有抗病毒活性。因此，我们旨在评估 DIG 和 OUA 对 SARS-CoV-2 感染的抗病毒活性。以纳摩尔浓度确定 DIG 和 OUA 的半最大抑制浓度（IC）。在感染后 48 小时（hpi），DIG、OUA 和瑞德西韦的单剂量治疗的子代病毒滴度分别比未处理的对照或氯喹低约 10、10 和 10 倍（>99%抑制）。此外，DIG 和 OUA 的治疗性治疗抑制了超过 99%的 SARS-CoV-2 复制，从而导致病毒在病毒生命周期的进入后阶段受到抑制。综上所述，这些结果表明 DIG 和 OUA 可能是 COVID-19 的一种替代治疗方法，对患有心血管疾病的患者可能具有额外的治疗效果。
