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