Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets

Author:

Park Su-Jin12,Yu Kwang-Min12,Kim Young-Il12,Kim Se-Mi12,Kim Eun-Ha12,Kim Seong-Gyu12,Kim Eun Ji1,Casel Mark Anthony B.12,Rollon Rare1,Jang Seung-Gyu1,Lee Min-Hyeok1,Chang Jae-Hyung1,Song Min-Suk12ORCID,Jeong Hye Won3,Choi Younho4ORCID,Chen Weiqiang4,Shin Woo-Jin4,Jung Jae U.4ORCID,Choi Young Ki12

Affiliation:

1. Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

2. Zoonotic Infectious Disease Research Center, Chungbuk National University, Cheongju, Republic of Korea

3. Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

4. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

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.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Dental and Craniofacial Research

National Research Foundation of Korea

Korea Research Institute of Bioscience and Biotechnology

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference24 articles.

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