Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.

中文翻译：

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海洋复方霉酚酸甲酯对甲型流感病毒的抑制作用及机制

甲型流感病毒（IAV）可引起包括人类、家禽和猪在内的多种动物感染和患病，并引起年度流行病，导致全世界数千人死亡和数百万人住院。因此，迫切需要开发高效、低毒的新型抗IAV药物。在这项研究中，海洋源性化合物霉酚酸甲酯 (MAE) 的抗 IAV 活性在体外和体内进行了深入研究。结果表明，MAE在体外可抑制不同甲型流感病毒株的复制，且细胞毒性较低。 MAE主要可以阻断IAV感染后吸附的一些步骤。 MAE 还可能通过激活细胞 Akt-mTOR-S6K 通路来抑制病毒复制。重要的是，口服MAE可以显着改善肺炎症状，降低肺部病毒滴度，提高小鼠的生存率，且优于奥司他韦的效果。综上所述，海洋化合物MAE在体外和体内均具有抗IAV作用，值得进一步研究以开发成新型抗IAV药物。