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Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2

Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, 72076 Tübingen, Germany
ImmunoLogik GmbH, 13507 Berlin, Germany
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrew Davidson
Viruses 2021, 13(4), 647;
Received: 7 December 2020 / Revised: 22 March 2021 / Accepted: 1 April 2021 / Published: 9 April 2021
(This article belongs to the Special Issue Pathogenesis of Human and Animal Coronaviruses)
While vaccination campaigns are ongoing worldwide, there is still a tremendous medical need for efficient antivirals against SARS-CoV-2 infection. Among several drug candidates, chloroquine (CQN) and hydroxychloroquine (H-CQN) were tested intensively, and any contentious therapeutic effect of both has been discussed controversially in the light of severe side effects and missing efficacy. Originally, H-CQN descended from the natural substance quinine, a medicinal product used since the Middle Ages, which actually is regulatory approved for various indications. We hypothesized that quinine also exerts anti-SARS-CoV-2 activity. In Vero cells, quinine inhibited SARS-CoV-2 infection more effectively than CQN, and H-CQN and was less toxic. In human Caco-2 colon epithelial cells as well as the lung cell line A549 stably expressing ACE2 and TMPRSS2, quinine also showed antiviral activity. In consistence with Vero cells, quinine was less toxic in A549 as compared to CQN and H-CQN. Finally, we confirmed our findings in Calu-3 lung cells, expressing ACE2 and TMPRSS2 endogenously. In Calu-3, infections with high titers of SARS-CoV-2 were completely blocked by quinine, CQN, and H-CQN in concentrations above 50 µM. The estimated IC50s were ~25 µM in Calu-3, while overall, the inhibitors exhibit IC50 values between ~3.7 to ~50 µM, dependent on the cell line and multiplicity of infection (MOI). Conclusively, our data indicate that quinine could have the potential of a treatment option for SARS-CoV-2, as the toxicological and pharmacological profile seems more favorable when compared to its progeny drugs H-CQN or CQN. View Full-Text
Keywords: SARS-CoV-2; quinine; COVID-19; antiviral SARS-CoV-2; quinine; COVID-19; antiviral
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MDPI and ACS Style

Große, M.; Ruetalo, N.; Layer, M.; Hu, D.; Businger, R.; Rheber, S.; Setz, C.; Rauch, P.; Auth, J.; Fröba, M.; Brysch, E.; Schindler, M.; Schubert, U. Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2. Viruses 2021, 13, 647.

AMA Style

Große M, Ruetalo N, Layer M, Hu D, Businger R, Rheber S, Setz C, Rauch P, Auth J, Fröba M, Brysch E, Schindler M, Schubert U. Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2. Viruses. 2021; 13(4):647.

Chicago/Turabian Style

Große, Maximilian, Natalia Ruetalo, Mirjam Layer, Dan Hu, Ramona Businger, Sascha Rheber, Christian Setz, Pia Rauch, Janina Auth, Maria Fröba, Ekkehard Brysch, Michael Schindler, and Ulrich Schubert. 2021. "Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2" Viruses 13, no. 4: 647.

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