The Ethanol Extract of Evodiae Fructus and Its Ingredient, Rutaecarpine, Inhibit Infection of SARS-CoV-2 and Inflammatory Responses

COVID-19, derived from SARS-CoV-2, has resulted in millions of deaths and caused unprecedented socioeconomic damage since its outbreak in 2019. Although the vaccines developed against SARS-CoV-2 provide some protection, they have unexpected side effects in some people. Furthermore, new viral mutations reduce the effectiveness of the current vaccines. Thus, there is still an urgent need to develop potent non-vaccine therapeutics against this infectious disease. We recently established a series of detecting platforms to screen a large library of Chinese medicinal herbs and phytochemicals. Here, we reveal that the ethanolic extract of Evodiae Fructus and one of its components, rutaecarpine, showed promising potency in inhibiting the activity of 3C-like (3CL) protease, blocking the entry of the pseudo-typed SARS-CoV-2 (including wild-type and omicron) into cultured cells. In addition, inflammatory responses induced by pseudo-typed SARS-CoV-2 were markedly reduced by Evodiae Fructus extract and rutaecarpine. Together our data indicate that the herbal extract of Evodiae Fructus and rutaecarpine are potent anti-SARS-CoV-2 agents, which might be considered as a treatment against COVID-19 in clinical applications.

Automated summary

COVID-19, caused by SARS-CoV-2, has had devastating impacts since its outbreak in 2019, leading to millions of deaths and unprecedented socioeconomic damage. Vaccines against SARS-CoV-2 have limitations and new viral mutations reduce their effectiveness, highlighting the urgent need for potent non-vaccine treatments. Researchers have identified the ethanolic extract of Evodiae Fructus and its component, rutaecarpine, as promising agents that inhibit the activity of 3C-like protease, block viral entry, and reduce inflammatory responses induced by SARS-CoV-2. These findings suggest that Evodiae Fructus extract and rutaecarpine could be considered for clinical applications in treating COVID-19.