Fujikane Aya, Fujikane Ryosuke, Sechi Yusuke, Nishi Akinori, Ishino Yoshizumi, Hiyoshi Tetsuya, Sakamoto Atsuhiko, Nabeshima Shigeki
Department of General Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Fukuoka Prefecture, Japan.
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Fukuoka Prefecture, Japan.
Microbiol Spectr. 2025 Jun 3;13(6):e0037125. doi: 10.1128/spectrum.00371-25. Epub 2025 Apr 30.
Maoto, a traditional herbal medicine widely prescribed in Japan, has been shown to be effective in the treatment of influenza virus infection, but the mechanisms of its antiviral action remain unclear. We previously demonstrated that maoto binds to respiratory syncytial virus (RSV) spike proteins, thereby inhibiting their entry into host cells. In this report, a similar experiment was done to determine if maoto and its components have an anti-infective effect on the influenza virus. Our results indicate that maoto binds to the hemagglutinin (HA) spike protein, inhibiting virus entry into host cells in a manner analogous to its antiviral effect on RSV. This hemagglutinin-binding effect was observed across influenza A(H1N1), A(H3N2), and B viruses, highlighting the broad-spectrum inhibitory potential of maoto against diverse viral strains. Furthermore, maoto, internalized by cells along with the influenza virus, binds to a cap-dependent endonuclease (polymerase acidic [PA] protein) that is crucial for viral replication and inhibits its nuclease activity. Among maoto's constituent crude drugs, Ephedrae Herba (EH) and Cinnamomi Cortex (CC) were found to bind to both hemagglutinin and PA, indicating that they are responsible for the anti-infective effect of maoto. Maoto is distinctive in its multiple points of antiviral action, exhibiting a broad spectrum of antiviral properties, which makes it a versatile therapeutic agent against various viral mutations.IMPORTANCEThe influenza virus is a formidable pathogen responsible for global pandemics that claim over 300,000 lives annually. Employing an ingenious evolutionary strategy, this virus undergoes constant mutation, deftly evading the action of therapeutic agents and sustaining its relentless impact. Maoto, a traditional herbal medicine, has long been known for its efficacy against viral infections and is frequently prescribed in Japan for the treatment of influenza; however, the precise mechanisms of its action remain unclear. Our study was done to elucidate the antiviral mechanisms of maoto against the influenza virus, presenting data that supports its unique potential as a therapeutic agent capable of flexibly adapting to mutations of the influenza virus. These findings pave the way for the development of new drugs and the expansion of therapeutic options.
麻黄汤是一种在日本广泛应用的传统草药，已被证明对治疗流感病毒感染有效，但其抗病毒作用机制尚不清楚。我们之前证明麻黄汤可与呼吸道合胞病毒（RSV）刺突蛋白结合，从而抑制其进入宿主细胞。在本报告中，我们进行了类似实验，以确定麻黄汤及其成分对流感病毒是否具有抗感染作用。我们的结果表明，麻黄汤可与血凝素（HA）刺突蛋白结合，以类似于其对RSV的抗病毒作用的方式抑制病毒进入宿主细胞。在甲型（H1N1）、甲型（H3N2）和乙型流感病毒中均观察到这种血凝素结合效应，突出了麻黄汤对多种病毒株的广谱抑制潜力。此外，麻黄汤与流感病毒一起被细胞内化后，会与对病毒复制至关重要的帽依赖性核酸内切酶（聚合酶酸性[PA]蛋白）结合，并抑制其核酸酶活性。在麻黄汤的组成生药中，发现麻黄（EH）和肉桂（CC）均能与血凝素和PA结合，表明它们是麻黄汤抗感染作用的原因。麻黄汤的独特之处在于其具有多个抗病毒作用点，表现出广泛的抗病毒特性，这使其成为对抗各种病毒突变的通用治疗剂。
流感病毒是一种强大的病原体，每年导致全球超过30万人死亡的大流行。该病毒采用巧妙的进化策略，不断发生突变，巧妙地逃避治疗药物的作用并持续产生严重影响。麻黄汤是一种传统草药，长期以来以其对病毒感染的疗效而闻名，在日本常用于治疗流感；然而，其确切作用机制尚不清楚。我们开展这项研究以阐明麻黄汤对流感病毒的抗病毒机制，提供的数据支持了其作为能够灵活适应流感病毒突变的治疗剂的独特潜力。这些发现为新药开发和治疗选择的扩展铺平了道路。
