The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters

Miorin, L.; Mire, C. E.; Ranjbar, S.; Hume, A. J.; Huang, J.; Crossland, N. A.; White, K. M.; Laporte, M.; Kehrer, T.; Haridas, V.; Moreno, E.; Nambu, A.; Jangra, S.; Cupic, A.; Dejosez, M.; Abo, K. A.; Tseng, A. E.; Werder, R. B.; Rathnasinghe, R.; Mutetwa, T.; Ramos, I.; Sainz de Aja, J.; Garcia de Alba Rivas, C.; Schotsaert, M.; Corley, R. B.; Falvo, J. V.; Fernandez-Sesma, A.; Kim, C.; Rossignol, J.-F.; Wilson, A. A.; Zwaka, T.; Kotton, D. N.; Mühlberger, E.; García-Sastre, A.; Goldfeld, A. E.

doi:10.1101/2022.02.08.479634

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bioRxiv · 10.1101/2022.02.08.479634

The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters

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Abstract

A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs.

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Miorin, L., Mire, C. E., Ranjbar, S., Hume, A. J., Huang, J., Crossland, N. A., White, K. M., Laporte, M., Kehrer, T., Haridas, V., Moreno, E., Nambu, A., Jangra, S., Cupic, A., Dejosez, M., Abo, K. A., Tseng, A. E., Werder, R. B., Rathnasinghe, R., Mutetwa, T., Ramos, I., Sainz de Aja, J., Garcia de Alba Rivas, C., Schotsaert, M., Corley, R. B., Falvo, J. V., Fernandez-Sesma, A., Kim, C., Rossignol, J.-F., Wilson, A. A., Zwaka, T., Kotton, D. N., Mühlberger, E., García-Sastre, A., Goldfeld, A. E.. 2022-02-09. The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters. https://doi.org/10.1101/2022.02.08.479634

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