Identification of Potential Antiviral Hops Compounds against Chikungunya Virus

Abstract

Chikungunya virus (CHIKV) is an arthropod-borne virus that belongs to the genus Alphavirus (family Togaviridae). CHIKV causes chikungunya fever, which is mostly characterized by fever, arthralgia and, sometimes, a maculopapular rash. The bioactive constituents of hops (Humulus lupulus, Cannabaceae), mainly acylphloroglucinols, known as well as α- and β-acids, exerted distinct activity against CHIKV, without showing cytotoxicity. For fast and efficient isolation and identification of such bioactive constituents, a silica-free countercurrent separation method was applied. The antiviral activity was determined by plaque reduction test and was visually confirmed by a cell-based immunofluorescence assay. All hops compounds demonstrated a promising post-treatment viral inhibition, except the fraction of acylphloroglucinols, in mixture. β-acids fraction of 125 µg/mL expressed the strongest virucidal activity (EC50 = 15.21 µg/mL), in a drug-addition experiment on Vero cells. Hypothesis for mechanism of action were proposed for acylphloroglucinols based on their lipophilicity and chemical structure. Therefore, inhibition of some steps of the protein kinase C (PKC) transduction cascades was also discussed.