The Antiviral Activity of Polyphenols

Abstract

Polyphenols are secondary metabolites produced by a large variety of plants. These compounds that comprise the class of phenolic acids, stilbenes, lignans, coumarins, flavonoids, and tannins have a wide range of employment, from food production to medical usages. Among the beneficial applications of polyphenols, their antiviral activity is gaining importance due to the increased prevalence of drug-resistant viruses such as herpes and hepatitis B viruses. In the present review, we provide an overview of the most promising or commonly used antiviral polyphenols and their mechanisms of action focusing on their effects on enveloped viruses of clinical importance (double-stranded linear or partially double-stranded circular DNA viruses, negative sense single-stranded RNA viruses with nonsegmented or segmented genomes, and positive sense single-stranded RNA viruses). The present work emphasizes the relevance of polyphenols, in particular epigallocatechin-3-gallate and resveratrol, as alternative or supportive antivirals. Polyphenols could interfere with virtually all steps of viral infection, from the adsorption to the release of viral particles. The activity of polyphenols against viruses is especially relevant given the risk of widespread outbreaks associated with viruses, remarked by the recent COVID-19 pandemic.

Keywords: antivirals; enveloped virus; polyphenols.

FIGURE 1

Overview of polyphenols. The basic structure of polyphenols (left column) with some of the most common examples for each class (right column). The main dietary sources for the represented polyphenols are provided in the boxes underneath the structures.

FIGURE 2

Overview of the viruses reported in the present review. Viruses are stratified by genome (DNA or RNA), presence or absence of an envelope, and type of genome (single‐ or double‐stranded, positive or negative sense). The families of the viruses reported in this review are indicated together with the species. CHIKV, chikungunya virus; DENV, dengue virus; EBOV, Ebola virus; FLUV, influenza virus; HBV, hepatitis B virus; HCoV, human coronavirus; HCV, hepatitis C virus; HHV, human herpesvirus; JEV, Japanese encephalitis virus; MERS‐CoV, Middle East respiratory syndrome coronavirus; MeV, measles virus; RSV, respiratory syncytial virus; RVFV, Rift Valley fever virus; SARS‐CoV, severe acute respiratory syndrome coronavirus; VACV, vaccinia virus; VSV, vesicular stomatitis Indiana virus; WNV, West Nile virus; ZIKV, Zika virus.

FIGURE 3

Summary of the antiviral activity of polyphenols. Overview of the viral infection pathways affected by polyphenols. The main aspects of the viral infection are depicted (round boxes) together with the polyphenols involved in the hindrance (green boxes) and the viruses affected (colored boxes). Viruses are further stratified by their genome (DNA or RNA) by a colored box (red or blue, respectively). CHIKV, chikungunya virus; CoV, coronavirus; DENV, dengue virus; EBOV, Ebola virus; FLUV, influenza virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HHV, human herpesvirus; JEV, Japanese encephalitis virus; MeV, measles virus; VACV, vaccinia virus; WNV, West Nile virus; ZIKV, Zika virus.

FIGURE 4

Biologically relevant residues of flavonoids. Basic structure of the flavan skeleton with numeration of the carbon atoms and identification of the two aromatic and the heterocyclic rings (A–C) with indication of the most relevant positions and their main substituents like hydroxyl groups (–OH), methoxy groups (–OMe), or –O‐glycosides, which are important for the antimicrobial activity of the flavonoids.