Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)?

Abstract

Much more serious than the previous severe acute respiratory syndrome (SARS) coronavirus (CoV) outbreaks, the novel SARS-CoV-2 infection has spread speedily, affecting 213 countries and causing ∼17,300,000 cases and ∼672,000 (∼+1,500/day) deaths globally (as of July 31, 2020). The potentially fatal coronavirus disease (COVID-19), caused by air droplets and airborne as the main transmission modes, clearly induces a spectrum of respiratory clinical manifestations, but it also affects the immune, gastrointestinal, hematological, nervous, and renal systems. The dramatic scale of disorders and complications arises from the inadequacy of current treatments and absence of a vaccine and specific anti-COVID-19 drugs to suppress viral replication, inflammation, and additional pathogenic conditions. This highlights the importance of understanding the SARS-CoV-2 mechanisms of actions and the urgent need of prospecting for new or alternative treatment options. The main objective of the present review is to discuss the challenging issue relative to the clinical utility of plants-derived polyphenols in fighting viral infections. Not only is the strong capacity of polyphenols highlighted in magnifying health benefits, but the underlying mechanisms are also stressed. Finally, emphasis is placed on the potential ability of polyphenols to combat SARS-CoV-2 infection via the regulation of its molecular targets of human cellular binding and replication, as well as through the resulting host inflammation, oxidative stress, and signaling pathways.

Keywords: complications; microbiota; oxidative stress; polyphenols; viral infection.

Fig. 1.

Main classes of polyphenols. Polyphenols are classified into flavonoids and nonflavonoids that contain a diverse group of compounds with a phenolic acid.

Fig. 2.

Genomic organization and structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [created with BioRender.com]. The genome sequencing includes two large genes, open reading frame (ORF)1A and ORF1B, which encode 1–16 nonstructural proteins constituting a replication–transcription complex, closely involved in the genome transcription and replication. The structural genes encode the following structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N). The additional accessory proteins are specific for SARS-CoV-2 in terms of number, genomic organization, sequence, and function. 3CL^pro, 3-chymotrypsin-like protease; UTR, untranslated region.

Fig. 3.

Replication cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the target cell [created with BioRender.com]. The illustration details the replication cycle of the virus starting from binding of the S Spike to the receptor angiotensin-converting enzyme 2 (ACE2) and other potential receptors. Through endosomal membrane fusion, the virus enters the cell and releases its RNA genome. Following transcription and translation, the products (viral structural and nonstructural proteins and genomic RNA) are assembled into virions, transported by vesicles, and released out of the target cell.

Fig. 4.

Potential cross-talk between gut microbiota and lungs during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [created with Servier Medical Art]. The gut–lung axis is bidirectional and able to induce changes in the blood and respective microbiota, illustrating the association of gut microbiota dysbiosis with local and distal pulmonary system. For example, the inflammation occurring in the pulmonary system leads to modifications in gut microbiota, and vice versa. LPS: Lipopolysaccharide.

Fig. 5.

Possible mechanisms of polyphenols against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The multiple biological properties may be actuated to counteract viral infection and related complications. 3CL^pro, 3-chymotrypsin-like protease; ACE2, angiotensin-converting enzyme 2; DPP4, dipeptidyl peptidase 4; TMPRSS2, transmembrane protease serine 2.

Fig. 6.

Beneficial effects of polyphenols against diverse disorders mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This illustration summarizes the main health benefits of polyphenols in pathological conditions, which can be built upon and produce beneficial results in the threatening coronavirus disease (COVID-19).