Waldy Yudha Perdana, Akeno Tsuneki-Tokunaga, Koyuki Atifa Rahmi, Alfredo A. Hinay, Kyosuke Kanai, Seiji Kageyama
Highly replicative influenza viruses have been linked to elevated nasopharyngeal viral load in patients, while in murine model these viruses are associated with amplified cytokine responses, and greater severity. In the present study, five anti-influenza agents—including four neuraminidase inhibitors (zanamivir, laninamivir, peramivir, and oseltamivir acid) and one polymerase acidic endonuclease inhibitor (baloxavir acid)—were evaluated against both a laboratory strain (PR8) and four clinical isolates lacking known resistance mutations. Madin-Darby Canine Kidney (MDCK) and A549 human lung epithelial cells were inoculated at 1x105 and 3x105 virus copies/mL, respectively, and exposed to varying concentrations of the drug for 72 hours. Subsequent analysis measured viral loads and infectious units. Both classes of antiviral drugs demonstrated substantial activity, particularly against strains that proliferate rapidly in vitro. While all tested anti-influenza drugs reduced viral particles production by approximately 50% in clinical isolates, achieving 90% suppression with neuraminidase inhibitors was limited to the PR8 laboratory strain. In A549 cell cultures, PR8 showed a 90% reduction in viral particles production with any of the compounds; however, neuraminidase inhibitors typically had diminished impact on clinical isolates. Notably, baloxavir acid consistently achieved robust suppression in both the PR8 strain and clinical isolates in MDCK and A549 cell lines. The present study finds that antiviral drugs can significantly impact highly replicative influenza viruses, but do not always suppress them to undetectable levels. Effectiveness varies by the epidemic strains, likely due to unknown genetic factors. Further research is needed to identify these traits and improve diagnosis and treatment. © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2026.
Division of Virology, Department of Microbiology and Immunology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan; Department of Clinical Microbiology, Faculty of Medicine, Universitas Brawijaya/Dr. Saiful Anwar Hospital, East Java Province, Malang, 65145, Indonesia; Clinical Microbiology Study Program, Faculty of Medicine, Universitas Brawijaya/Dr. Saiful Anwar Hospital, East Java Province, Malang, 65145, Indonesia; Division of Pathogenesis and Disease Control, Avian Infectious Disease and Global Health Research Center, Tottori University, 4-101 Koyama-cho Minami, Tottori, 680-8550, Japan
