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.

Antiviral Activity and Molecular Dynamics Simulation of Hops Compounds against Oropouche Virus (Peribunyaviridae)

“…A 72 h post-treatment by a MTT cytotoxicity test assay as applied to analyze the Vero cell toxicity [37]. As previously described, the fractions displayed cell viability well above 50% at the concentration of 250 µg/mL and and lower concentrations tested [12]. The CC 50 for all four fractions in this assay displayed cell viability above 50% at the highest concentration; thus, no CC 50 value could be measured (Table 1 and Figure S1 in Supplementary Materials).…”

“…The present methodology was executed following established procedures, as previously reported [ 12 , 15 , 16 ]. In brief, Vero cells (4 × 10 4 /well) were cultured in 96-well plates with MEM and subjected to treatment with each of the five fractions obtained after CCC (countercurrent chromatography) purification, a liquid–liquid chromatography technique.…”

“…Subsequently, the cells were treated with hops fractions, DMSO (used as a vehicle control), or MEM supplemented with 2% (v/v) FBS (used as a viral control). At specified time points (12,24, or 48 h postinfection), cell supernatants were collected to determine viral titers using a plaque-forming assay, as described below. The range tested was 125 µg/mL to 31.25 µg/mL.…”

“…Considering these characteristics, we were motivated to explore the antiviral activity of the major hop compounds. Our previous research into the antiviral properties of key compounds—acylphloroglucinols and xanthohumol, derived from Humulus lupulus L. (Cannabaceae) against the chikungunya virus, showed highly promising results [ 12 ]. This widely recognized ingredient in the global brewing industry inspired us to further explore the potential antiviral effects of these major compounds against various types of viral strains.…”

ECHOPvir: A Mixture of Echinacea and Hop Extracts Endowed with Cytoprotective, Immunomodulatory and Antiviral Properties

“…Along with Echinacea, hop cones were also reported to possess antiviral properties [26,100,101]. Recently, Bouback et al showed that a boiled water extract from the dried whole plant of H. lupulus possessed anticoronaviral properties against both MERS-CoV and SARS-CoV-2, blocking the viral ability to infect and replicate inside the host cells: these effects are mainly ascribed to its polyphenolic compounds [102].…”