<p>Influenza virus causes worldwide outbreaks and seasonal epidemics, posing a severe threat to public health and social development. Effective prevention and treatment of influenza infections remain major challenge for global healthcare. In this study, we observed that taurolidine effectively inhibited the proliferation of several human or animal influenza virus strains and protected mice from lethal-infection. Taurolidine treatment decreased the viral titer in the lungs of infected mice, reduced the ratio of immune cells, and alleviated lung pathology. Additionally, taurolidine treatment attenuated the rise of blood pressure, pulse wave velocity, and pulmonary aortic thickness in a mouse model for influenza virus infection. We also found that taurolidine significantly decreased intracellular Ca²⁺ concentration and effectively alleviated pulmonary artery vasoconstriction during influenza virus infection. Mechanistically, we observed that vascular smooth muscle contraction signaling pathway was significantly enriched, and taurolidine inhibited the activation of the MLCK/p-MLC pathway. Taking together, these findings confirm the effectiveness of taurolidine as an antiviral agent and highlight its important roles in mitigating host immune cell infiltration and vasoconstriction induced by influenza virus infection.</p>