Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets
Su-Jin Park, Kwang-Min Yu, Young‐Il Kim, Se-Mi Kim, Eun-Ha Kim, Seong-Gyu Kim, Eun Ji Kim, Mark Anthony B. Casel, Rare Rollon, Seung‐Gyu Jang, Minhyeok Lee, Jae-Hyung Chang, Min‐Suk Song, Hye Won Jeong, Younho Choi, Weiqiang Chen, Woo-Jin Shin, Jae U. Jung, Young Ki Choi
Abstract
The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.