Tannins as therapeutic agents against SARS-CoV-2

In a recent review published in the International Journal of Biological Sciences, researchers reviewed tannins as therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

The unprecedented increase in SARS-CoV-2 infections across the globe has warranted the development of novel anti-SARS-CoV-2 agents. Researchers have suggested tannin compounds for limiting SARS-CoV-2 propagation. However, due to the structural diversity of tannin derivates, the potential use of tannins in the prevention and management of coronavirus disease 2019 (COVID-19) has not been well characterized.

About the review

In the present study, researchers reviewed the potential role of natural tannins in managing SARS-CoV-2 infections.

Introduction

Tannins are polyphenol compounds derived from wood, bark, leaves, roots, fruits, and seeds of several plants and can be classified into four different categories viz. condensed tannins, hydrolyzable tannins, phlorotannins, and complex tannins. Hydrolyzable tannins can be further subclassified as tannic acid (TA) or gallotannins and ellagitannins (e.g., punicalagin). Condensed tannins include catechins, procyanidins and proanthocyanidins. The most abundant tannins are condensed tannins followed by hydrolyzable tannins. Phlorotannins are rare and mainly present mainly in brown macroalgae.

In general, fruits such as pomegranates, apples, persimmons, grapes, bananas, guavas, cashew apples, blackberries, chokeberries, and raspberries have high tannin content. Most tannins derived from grapes are condensed tannins, and the estimated TA content in grape seeds is 4.1g/100g. In berries and grapes, 20% and 80% of tannin compounds are derived from the skin and seed, respectively, and 60% of tannins in wines are extracted from the skin of grapes.

Biological properties of tannins

Previous studies have shown that consumption of red wines containing 200 mg per day of procyanidins improved skin moisturization and whitening among healthy women aged 30 to 60 within 12 weeks. Further, daily supplements of polyphenols and resveratrol in 136mg and 19.2 mg concentrations, respectively, isolated from red wines for eight weeks increased sensitivity to insulin and reduced serum triglyceride (TG) and low-density lipoprotein (LDL) levels among individuals who did not have diabetes.

Dietary TA supplementations have been effective in behavioral and cognitive dysfunctions by inhibiting amyloidogenic precursor proteins processing, decreasing β-amyloid deposits in cerebral blood vessels, and decreasing neuro-inflammation in Alzheimer-like transgenic murine models. TA catechol compounds scavenge reactive oxygen species (ROS) and thereby contribute to the anti-cancer and anti-inflammatory properties of TA.

TA has protected rat renal tissues from post-ischemia-reperfusion injuries due to oxidative stress via NRF2 (nuclear factor erythroid-2- related factor 2) activation. Subcutaneous TA administrations reduced fibrosis in myocardial tissue and reduced levels of mediators of apoptosis such as TLR4 (toll-like receptor 4), NF-κB (nuclear factor kappa B), Bcl-2 (B-cell lymphoma-2), Bax (Bcl-2-associated protein) and the p38 kinase levels (that respond to stress) in isoproterenol-induced mice with myocardial fibrosis.

In addition, TA decreased renal injury and levels of cytokine molecules such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6,8 in rats. It has been reported that TA enhances chemotherapy-induced apoptosis. Persimmon-derived tannins have demonstrated efficacy against viruses such as the herpes simplex virus-1 (HSV-1), vesicular stomatitis virus (VSV), and influenza virus.

Tannins as anti-SARS-CoV-2 agents

Orally administered tannins extracted from chestnut and quebracho with B12 vitamin supplementations and standard treatment regimens have decreased TNF-α and MIP-1α (macrophage inflammatory protein-1α) levels among individuals hospitalized due to COVID-19. Additionally, TA can potently inhibit M^pro/3CL^pro (main protease/3-chymotrypsin-like cysteine protease, and TMPRSS2 (transmembrane protease serine 2) which are essential proteins for SARS-CoV-2 propagation. Similar activities have been observed by punicalaginin and proanthocyanidins in vitro.

In Syrian hamsters, oral gavage-administered persimmon-derived tannins suppressed SARS-CoV-2 titers, reduced the severity of COVID-19-associated pneumonia, and reduced the expression of inflammation-related genes such as interferon-gamma (IFN-γ). Green tea-derived tannins have inhibited SARS-CoV-2 replication in vitro and persist in pharyngeal mucosae for one-hour post-administration by throat sprays.

Furthermore, hydrolyzable tannins such as castalin and tercatain have been reported to possess potential anti-SARS-CoV-2 action by inhibiting M^pro/3CL^pro activity. Orally administered TA isomers have demonstrated efficacy against SARS-CoV-2 variants such as Delta and Omicron; however, clinical trials are necessary for the translation of TA isomers as routine anti-SARS-CoV-2 therapeutic agents.

Conclusions

Studies included in the present review underpin the use of tannins in the management of infections that cause metabolic, immunological, and cognitive dysfunctions and for cancer protection via reduction of oxidative stress and inflammatory cytokine levels. In addition, several studies have supported the use of tannins, especially TA, as safe and effective antiviral agents to combat and overcome COVID-19 and future pandemics.

Natural sources of tannins such as fruits and tea may be tapped to develop effective medications against the existing and rapidly SARS-CoV-2 variants, and tannins may be incorporated into daily diets for protection against SARS-CoV-2. Moreover, tannin compounds may be used in combination with Food and Drug Administration (FDA)-authorized drugs for enhanced efficacy against SARS-CoV-2 and other viruses.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.