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Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2.
Nature. 2020 09; 585(7826):588-590.Nat

Abstract

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 Vero1-3. Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, 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.

Authors+Show Affiliations

Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. mhoffmann@dpz.eu. Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany. mhoffmann@dpz.eu.Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. German Centre for Infection Research, associated partner Charité, Berlin, Germany.Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany.Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. German Centre for Infection Research, associated partner Charité, Berlin, Germany. Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russia.Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. German Centre for Infection Research, associated partner Charité, Berlin, Germany.Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. spoehlmann@dpz.eu. Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany. spoehlmann@dpz.eu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32698190

Citation

Hoffmann, Markus, et al. "Chloroquine Does Not Inhibit Infection of Human Lung Cells With SARS-CoV-2." Nature, vol. 585, no. 7826, 2020, pp. 588-590.
Hoffmann M, Mösbauer K, Hofmann-Winkler H, et al. Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature. 2020;585(7826):588-590.
Hoffmann, M., Mösbauer, K., Hofmann-Winkler, H., Kaul, A., Kleine-Weber, H., Krüger, N., Gassen, N. C., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature, 585(7826), 588-590. https://doi.org/10.1038/s41586-020-2575-3
Hoffmann M, et al. Chloroquine Does Not Inhibit Infection of Human Lung Cells With SARS-CoV-2. Nature. 2020;585(7826):588-590. PubMed PMID: 32698190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. AU - Hoffmann,Markus, AU - Mösbauer,Kirstin, AU - Hofmann-Winkler,Heike, AU - Kaul,Artur, AU - Kleine-Weber,Hannah, AU - Krüger,Nadine, AU - Gassen,Nils C, AU - Müller,Marcel A, AU - Drosten,Christian, AU - Pöhlmann,Stefan, Y1 - 2020/07/22/ PY - 2020/05/08/received PY - 2020/07/16/accepted PY - 2020/7/23/pubmed PY - 2020/10/6/medline PY - 2020/7/23/entrez SP - 588 EP - 590 JF - Nature JO - Nature VL - 585 IS - 7826 N2 - 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 Vero1-3. Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32698190/Chloroquine_does_not_inhibit_infection_of_human_lung_cells_with_SARS_CoV_2_ L2 - https://doi.org/10.1038/s41586-020-2575-3 DB - PRIME DP - Unbound Medicine ER -