The efficacy and mechanism of salmeterol against influenza A virus in vitro and in vivo.

Influenza A virus (IAV) is the most harmful pathogen to human beings among the various subtypes of influenza virus, which can lead to immune response, cause serious inflammation and damage to the lung. Salmeterol is a candidate compound with anti-IAV activity screened by virtual network proximity predication. In this paper, we further evaluated the pharmacodynamics of salmeterol against IAV in vivo and in vitro. The results showed that salmeterol could inhibit the activity of three IAV strains (H1N1, H3N2 and H1N1 strain resistant to oseltamivir and amantadine) in the MDCK cells. In vivo, salmeterol could improve the survival state of infected mice, and further mechanism studies shown that salmeterol could improve the pathological characteristics of the lungs, reduce the loads of virus and the expression of M2 and IFITM3 proteins in the lungs of mice. In addition, salmeterol could inhibit the formation of NLRP3 inflammasome, thus reducing the production of the TNF-α, IL-6 and MCP-1 and alleviating inflammatory symptoms. Further results showed that salmeterol can protect A549 cells from cytopathic effect caused by IAV and reduce the production of inflammasome by decreasing the expression of RIG-1 in A549 cells. Finally, salmeterol could improve the spleen morphology and significantly increase the ratio of lymphocyte CD4/CD8 to improve immune function of infected mice. In our study, it is confirmed that salmeterol has certain anti-IAV activity through pharmacodynamic study in vivo and in vitro, which lays an important research foundation for the new indication of salmeterol and discovery of new drug against IAV.