Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2
Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2
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DOI：
10.1038/s41586-020-2575-3
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发表时间：
2020-07-22
期刊：
影响因子：
64.8
通讯作者：
Poehlmann, Stefan
中科院分区：
文献类型：
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作者：
Hoffmann, Markus;Moesbauer, Kirstin;Poehlmann, Stefan
TMPRSS 2-一种激活SARS-CoV-2进入细胞的蛋白酶-的表达使SARS-CoV-2对氯喹不敏感。由严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行与全球超过78万例死亡有关（截至2020年8月20日）。为了快速开发抗病毒干预措施，用于治疗不相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，因为它抑制SARS-CoV-2在非洲绿色猴肾衍生细胞系Vero（1-3）中的传播。在这里，我们显示了TMPRSS 2的工程表达，一种激活SARS-CoV-2进入肺细胞的细胞蛋白酶（4），使SARS-CoV-2感染的Vero细胞对氯喹不敏感。此外，我们报告说，氯喹不阻断感染与SARS冠状病毒-2在TMPRSS 2表达的人肺细胞系Calu-3。这些结果表明，氯喹靶向的病毒活化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的传播。
Expression of TMPRSS2-a protease that activates SARS-CoV-2 for entry into cells-renders SARS-CoV-2 insensitive to chloroquine.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.