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Abstract
Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza.
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1 Korea University, Department of Pharmacy, College of Pharmacy, Sejong, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678); Chonnam National University, Laboratory Animal Medicine, College of Veterinary Medicine, Gwangju, Republic of Korea (GRID:grid.14005.30) (ISNI:0000 0001 0356 9399)
2 Korea University, Department of Pharmacy, College of Pharmacy, Sejong, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678)
3 Korea Disease Control and Prevention Agency, Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Health, Cheongju, Republic of Korea (GRID:grid.415482.e) (ISNI:0000 0004 0647 4899)
4 Korea University, Department of Pharmacy, College of Pharmacy, Sejong, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678); Korea Disease Control and Prevention Agency, Division of Acute Viral Diseases, Center for Emerging Virus Research, National Institute of Health, Cheongju, Republic of Korea (GRID:grid.415482.e) (ISNI:0000 0004 0647 4899)
5 Chungbuk National University, Department of Pharmaceutics, College of Pharmacy, Cheongju, Republic of Korea (GRID:grid.254229.a) (ISNI:0000 0000 9611 0917)