The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2
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Curated by eLife
eLife assessment
This fundamental work provides preclinical evidence to support that natural tannins derived from grapeseed can inhibit or prevent infection by the SARS-CoV-2 viruses. The evidence provided is mostly solid to convincing and supports the conclusions. This work will be of broad interest to cell biologists and physicians.
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Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 Vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention.
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eLife assessment
This fundamental work provides preclinical evidence to support that natural tannins derived from grapeseed can inhibit or prevent infection by the SARS-CoV-2 viruses. The evidence provided is mostly solid to convincing and supports the conclusions. This work will be of broad interest to cell biologists and physicians.
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Reviewer #1 (Public Review):
I feel that this study has potentially high public health significance and should be made known to the public, especially the usefulness of a natural chemical product, oligomeric proanthocyanidins, in preventing SARS-CoV2 infection. The studies are very well designed, using the first 5 figures to compare carefully the effects of tannic acid, punicalagin, and oligomeric proanthocyanidins in disrupting the interaction of the virus with host cells and in inhibiting the enzymatic activity of transmembrane serine protease 2 required for viral entry. I am especially impressed by the work done in Figures 6 and 7 in which the investigators put their efforts into quantitating the amounts of oligomeric proanthocyanidins, tannic acid, and punicalagin present in the grape seed, peel, flesh as well as juice. I also …
Reviewer #1 (Public Review):
I feel that this study has potentially high public health significance and should be made known to the public, especially the usefulness of a natural chemical product, oligomeric proanthocyanidins, in preventing SARS-CoV2 infection. The studies are very well designed, using the first 5 figures to compare carefully the effects of tannic acid, punicalagin, and oligomeric proanthocyanidins in disrupting the interaction of the virus with host cells and in inhibiting the enzymatic activity of transmembrane serine protease 2 required for viral entry. I am especially impressed by the work done in Figures 6 and 7 in which the investigators put their efforts into quantitating the amounts of oligomeric proanthocyanidins, tannic acid, and punicalagin present in the grape seed, peel, flesh as well as juice. I also appreciate the translational application in which the investigators prepared grape seed extract capsules (200 mg and 400 mg), recruited healthy human subjects to take these capsules once or twice, and showed that the sera from randomized human subjects taking grape seed extract capsules indeed exert does-dependent and time-dependent activities in suppressing the infection rate of various SARS-CoV2 variants using in vitro studies. The study in Figure 7 is indeed very well-designed and quite elegant. The manuscript is also well-written.
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Reviewer #2 (Public Review):
Chen et. al investigated the effects of natural tannins, proanthocyanidins, and punicalagin, against infection by the SARS-CoV-2 virus and its variants. The authors found that these two compounds affect different parts of the SARS-CoV-2 viral infection mechanisms, namely that punicalagin may act ACE2-spike protein interaction and repress Main protease activity, whereas tannic acid and OPC inhibits TMPRSS2 activity. Additionally, the authors show that these tannic compounds can act upon multiple variants of the virus, which suggests a pan-inhibitory effect on SARS-CoV-2 viruses. The studies performed herein present a novel alternative to inhibiting viral infection by SARS-CoV-2 which may be of interest to patients with concerns about reinfection.
The conclusions of this paper are mostly well supported by …
Reviewer #2 (Public Review):
Chen et. al investigated the effects of natural tannins, proanthocyanidins, and punicalagin, against infection by the SARS-CoV-2 virus and its variants. The authors found that these two compounds affect different parts of the SARS-CoV-2 viral infection mechanisms, namely that punicalagin may act ACE2-spike protein interaction and repress Main protease activity, whereas tannic acid and OPC inhibits TMPRSS2 activity. Additionally, the authors show that these tannic compounds can act upon multiple variants of the virus, which suggests a pan-inhibitory effect on SARS-CoV-2 viruses. The studies performed herein present a novel alternative to inhibiting viral infection by SARS-CoV-2 which may be of interest to patients with concerns about reinfection.
The conclusions of this paper are mostly well supported by data, but some aspects of the data analysis need to be clarified and extended.
All compounds should be tested in vivo to test not only safety but efficacy and whether these compounds elicit any acute liver toxicity when administered in proposed doses.
Efficacy in vaccinated patients would be of great interest, especially since many reinfections occur in the vaccinated population (especially by variants such as Delta).
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