The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2 in vitro

The 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 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. HighlightsO_LIOPCs and Punicalagin had inhibitory activity against omicron variants of SARS-CoV-2 infection. C_LIO_LIOPCs serve as a dual inhibitor of the viral Mpro and the cellular TMPRSS2 protease. C_LIO_LIPunicalagin possesses the most potent activity to suppress the Mpro and block the interaction of the viral spike protein and human ACE2. C_LIO_LIOPCs-enriched grape seed extractant exhibited inhibitory activities for viral entry of wild-type and other variants of SARS-CoV-2. C_LIO_LIThe daily intake of grape seed extractants may be able to prevent SARS-CoV-2 infection. C_LI