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

Große M, Ruetalo N, Layer M, Hu D, Businger R, Rheber S, Setz C, Rauch P, Auth J, Froeba M, Brysch E, Schindler M, Schubert U (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Viruses MDPI

Book Volume: 13

Journal Issue: 4

DOI: 10.3390/v13040647

Abstract

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 mu M. The estimated IC(50)s were similar to 25 mu M in Calu-3, while overall, the inhibitors exhibit IC50 values between similar to 3.7 to similar to 50 mu M, 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.

Authors with CRIS profile

Maximilian Große Institute of Clinical and Molecular Virology Christian Setz Institute of Clinical and Molecular Virology Janina Auth Professur für Virologie Ulrich Schubert Professur für Virologie

Involved external institutions

Universitätsklinikum Tübingen DE Germany (DE) ImmunoLogik GmbH DE Germany (DE)

How to cite

APA:

Große, M., Ruetalo, N., Layer, M., Hu, D., Businger, R., Rheber, S.,... Schubert, U. (2021). Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2. Viruses, 13(4). https://dx.doi.org/10.3390/v13040647

MLA:

Große, Maximilian, et al. "Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2." Viruses 13.4 (2021).

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