Influenza is a threat to humans and some animal species. The 1918 ‘Spanish’ H1N1 influenza epidemic caused 20 to 50 million deaths in less than a year (Loo and Gale, 2007; Tumpey et al., 2005). The recent 2013 H7N9 outbreak also caused significant morbidity and mortality (Yang et al., 2014). Its frequent reassortment causes high mortality and burdens the healthcare system (Russell et al., 2008). Chinese herbs are a valuable source of antiviral agents, and researchers have found several anti-influenza agents from traditional Chinese medicines (TCMs). Most anti-influenza herbs have heat-clearing and detoxifying properties, controlling influenza virus infection by directly inhibiting viral growth and regulating subsequent immune responses (Ge et al., 2010).

Fu Rong Ye (FRY, cotton rose hibiscus leaf, Hibiscus mutabilis L.) is the leaf of Hibiscus mutabilis L., from the Malvaceae family. Chinese medical literatures describe the actions of FRY as “clearing lung heat, cooling the blood and expelling toxins, resolving edema and alleviating pain”. The Drug Standard of the Ministry of Health of the People's Republic of China lists Fupo Ganmao Granules as a treatment for the common cold; FRY, the major herbal component, targets the symptoms of high fever, sore throat, and headache (Xu et al., 2019). Our preliminary anti-influenza virus agent screening showed that FRY aqueous extract effectively inhibited the growth of the A/WSN/33(H1N1) virus. However, there has been no study addressing the anti-influenza virus activity and mechanism of FRY. In light of this, we aimed to find and characterize the anti-influenza virus components of this herb and explain their mechanism.