Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pH-independent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy.

中文翻译：

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芙蓉茶提取物对人类甲型流感病毒的抗病毒活性主要依赖于酸性pH，但部分依赖于低pH依赖性机制。

甲型流感病毒（IAV）感染一直是世界范围内主要的死亡原因之一。需要有效的疗法和疫苗接种来控制病毒的扩张。然而，当前的抗IAV药物具有诱导抗药性病毒出现的风险。尽管鼻内施用完整的灭活病毒疫苗可以诱导有效的保护性免疫，但是福尔马林和β-丙内酯是目前使用的有害的灭活剂。在这里，我们分析了芙蓉（芙蓉sabdariffa L.）提取物抗人IAV，并评估了其作为新型抗IAV药物和整个灭活疫苗的安全灭活剂的潜力。体外研究表明，芙蓉茶提取物的pH值为酸性，其快速有效的抗病毒活性在很大程度上取决于酸性pH值。此外，小鼠研究表明，酸性提取物对于治疗或疫苗接种目的均无效。但是，芙蓉茶提取物和原儿茶酸（提取物的主要成分之一）不仅显示出强效的酸依赖性抗病毒活性，而且还显示出弱的低pH依赖性活性。低pH依赖性活性不影响免疫优势血凝素蛋白的构象。尽管这种低pH依赖性的活性非常有限，它可能适合于药物和疫苗接种，因为这种活性不受中性血液环境的影响，并且不会失去血凝素的抗原性。对低pH依赖性抗病毒机制的进一步研究以及增强抗病毒活性的尝试可能会建立一种新颖的抗IAV治疗和疫苗接种策略。