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-pHindependent 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. Keywords Acidic pH • Anti-human influenza A viral activity • Antiviral drug therapy • Hibiscus tea extract • Natural substance • Whole inactivated vaccine
Chiral primary β‐amino alcohols, constuting adjacently positioned Brønsted base and Brønsted acid sites, are emerging as very valuable bifunctional organocatalysts in a wide array of asymmetric organic transformations. Primary β‐amino alcohols represent inexpensive alternatives to other primary amino organocatalysts such as chiral diamines and cinchona‐alkaloid‐derived primary amines, being easy to synthesize and air‐stable and offering the potential for introduction of different functional groups and also for alteration of steric sites. Here we reveal the catalytic use of simple primary β‐amino alcohols and their derivatives as organocatalysts in Diels–Alder cycloaddition, aldol condensation, Michael addition, 1,3‐dipolar cycloaddition, the Morita–Baylis–Hillman reaction, cascade cyclization, allylation of isatins, Friedel–Crafts alkylation and epoxidation of olefins.
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