PT  - JOURNAL ARTICLE
AU  - Lisa Miorin
AU  - Chad E. Mire
AU  - Shahin Ranjbar
AU  - Adam J. Hume
AU  - Jessie Huang
AU  - Nicholas A. Crossland
AU  - Kris M White
AU  - Manon Laporte
AU  - Thomas Kehrer
AU  - Viraga Haridas
AU  - Elena Moreno
AU  - Aya Nambu
AU  - Sonia Jangra
AU  - Anastasija Cupic
AU  - Marion Dejosez
AU  - Kristine A. Abo
AU  - Anna E. Tseng
AU  - Rhiannon B. Werder
AU  - Raveen Rathnasinghe
AU  - Tinaye Mutetwa
AU  - Irene Ramos
AU  - Julio Sainz de Aja
AU  - Carolina Garcia de Alba Rivas
AU  - Michael Schotsaert
AU  - Ronald B. Corley
AU  - James V. Falvo
AU  - Ana Fernandez-Sesma
AU  - Carla Kim
AU  - Jean-François Rossignol
AU  - Andrew A. Wilson
AU  - Thomas Zwaka
AU  - Darrell N. Kotton
AU  - Elke Mühlberger
AU  - Adolfo García-Sastre
AU  - Anne E. Goldfeld
TI  - The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters
AID  - 10.1101/2022.02.08.479634
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.08.479634
4099  - http://biorxiv.org/content/early/2022/02/09/2022.02.08.479634.short
4100  - http://biorxiv.org/content/early/2022/02/09/2022.02.08.479634.full
AB  - 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.Competing Interest StatementThe AG-S laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, and Merck outside of the reported work. AG-S has consulting agreements for the following companies involving cash and/or stock outside of the reported work: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, and Pfizer. AG-S is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. J-FR is an employee of, and owns an equity interest in, Romark, L.C. The authors claim no other competing interests.