Abstract: Prophylactic Effect of Ivermectin on SARS-CoV-2 Induced Disease in a Syrian Hamster Model Takayuki Uematsu (  tuematsu@insti.kitasato-u.ac.jp ) Kitasato University Medical Center Tomomi Takano Department of Veterinary Medicine, Kitasato University Hidehito Matsui Ōmura Satoshi Memorial Institute, Kitasato University Noritada Kobayashi Kitasato University Medical Center Hideaki Hanaki Ōmura Satoshi Memorial Institute, Kitasato University Article Keywords: Posted Date: September 15th, 2022 DOI: https://doi.org/10.21203/rs.3.rs-2012940/v1 License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/14 Abstract COVID-19, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity. Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In the present study, we investigated the in vivo effects of ivermectin in a hamster model of SARS-CoV-2 infection. The results of the present study demonstrate oral administration of ivermectin prior to SARS-CoV-2 infection in hamsters was associated with decreased weight loss and pulmonary inflammation. In addition, the administration of ivermectin reduced pulmonary viral titers and mRNA expression level of proinflammatory cytokines associated with severe COVID-19 disease. The administration of ivermectin rapidly induced the production of virus-specific neutralizing antibodies in the late stage of viral infection. Zinc concentrations leading to immune quiescence were also significantly higher in the lungs of ivermectin-treated hamsters compared to controls. These results indicate that ivermectin may have efficacy in reducing the development and severity of COVID-19 by affecting host immunity in a hamster model of SARS-CoV-2 infection.