The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with more than 780,000 deaths worldwide (as of 20 August 2020). To develop antiviral interventions quickly, drugs used for the treatment of unrelated diseases are currently being repurposed to treat COVID-19. Chloroquine is an anti-malaria drug that is used for the treatment of COVID-19 as it inhibits the spread of SARS-CoV-2 in the African green monkey kidney-derived cell line Vero 1 – 3 . Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells 4 , renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. Moreover, we report that chloroquine does not block infection with SARS-CoV-2 in the TMPRSS2-expressing human lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not active in lung cells and is unlikely to protect against the spread of SARS-CoV-2 in and between patients. Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

中文翻译：

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氯喹不能抑制 SARS-CoV-2 对人肺细胞的感染

由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行已导致全球超过 780,000 人死亡（截至 2020 年 8 月 20 日）。为了快速开发抗病毒干预措施，用于治疗无关疾病的药物目前正在重新用于治疗 COVID-19。氯喹是一种抗疟疾药物，用于治疗 COVID-19，因为它可以抑制 SARS-CoV-2 在非洲绿猴肾衍生细胞系 Vero 1-3 中的传播。在这里，我们展示了 TMPRSS2（一种激活 SARS-CoV-2 进入肺细胞的细胞蛋白酶）的工程表达 4，使 Vero 细胞的 SARS-CoV-2 感染对氯喹不敏感。而且，我们报告说，在表达 TMPRSS2 的人肺细胞系 Calu-3 中，氯喹不能阻断 SARS-CoV-2 的感染。这些结果表明，氯喹靶向一种病毒激活途径，该途径在肺细胞中不活跃，不太可能防止 SARS-CoV-2 在患者体内和患者之间传播。TMPRSS2（一种激活 SARS-CoV-2 进入细胞的蛋白酶）的表达使 SARS-CoV-2 对氯喹不敏感。