Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2.

The Omicron subvariants of SARS-CoV-2 have multiple mutations in the S-proteins and show high transmissibility. We previously reported that tea catechin (-)-epigallocatechin gallate (EGCG) and its derivatives including theaflavin-3,3'-di-O-digallate (TFDG) strongly inactivated the conventional SARS-CoV-2 by binding to the receptor binding domain (RBD) of the S-protein. Here we show that Omicron subvariants were effectively inactivated by green tea, Matcha, and black tea. EGCG and TFDG strongly suppressed infectivity of BA.1 and XE subvariants, while effect on BA.2.75 was weaker. Neutralization assay showed that EGCG and TFDG inhibited interaction between BA.1 RBD and ACE2. In silico analyses suggested that N460K, G446S and F490S mutations in RBDs crucially influenced the binding of EGCG/TFDG to the RBDs. Healthy volunteers consumed a candy containing green tea or black tea, and saliva collected from them immediately after the candy consumption significantly decreased BA.1 virus infectivity in vitro. These results indicate specific amino acid substitutions in RBDs that crucially influence the binding of EGCG/TFDG to the RBDs and different susceptibility of each Omicron subvariant to EGCG/TFDG. The study may suggest molecular basis for potential usefulness of these compounds in suppression of mutant viruses that could emerge in the future and cause next pandemic.

Milk Casein Inhibits Effect of Black Tea Galloylated Theaflavins to Inactivate SARS-CoV-2 In Vitro.

Continuing caution is required against the potential emergence of SARS-CoV-2 novel mutants that could pose the next global health and socioeconomical threats. If virus in saliva can be inactivated by a beverage, such a beverage may be useful because the saliva of infected persons is the major origin of droplets and aerosols that mediate human-to-human viral transmission. We previously reported that SARS-CoV-2 was significantly inactivated by treatment in vitro with tea including green tea and black tea. Catechins and its derived compounds galloylated theaflavins (gTFs) bound to the receptor-binding domain (RBD) of the S-protein and blocked interaction between RBD and ACE2. Black tea is often consumed with sugar, milk, lemon juice, etc., and it remains unclarified whether these ingredients may influence the anti-SARS-CoV-2 effect of black tea. Here, we examined the effect of black tea on Omicron subvariants in the presence of these ingredients. The infectivity of Omicron subvariants was decreased to 1/100 or lower after treatment with black tea for 10 s. One or two teaspoons of milk (4~8 mL) completely blocked the anti-viral effect of a cup of tea (125 mL), whereas an addition of sugar or lemon juice failed to do so. The suppressive effect was dose-dependently exerted by milk casein but not whey proteins. gTFs were coprecipitated with casein after acidification of milk-supplemented black tea, strongly suggesting the binding of gTFs to casein. The present study demonstrates for the first time that an addition of milk cancelled the anti-SARS-CoV-2 effect of black tea due to binding of casein to gTFs.

Rapid Inactivation In Vitro of SARS-CoV-2 in Saliva by Black Tea and Green Tea.

Saliva plays major roles in the human-to-human transmission of SARS-CoV-2. If the virus in saliva in SARS-CoV-2-infected individuals can be rapidly and efficiently inactivated by a beverage, the ingestion of the beverage may attenuate the spread of virus infection within a population. Recently, we reported that SARS-CoV-2 was significantly inactivated by treatment with black tea, green tea, roasted green tea and oolong tea, as well as their constituents, (-) epigallocatechin gallate (EGCG), theasinensin A (TSA), and galloylated theaflavins. However, it remains unclear to what extent tea inactivates the virus present in saliva, because saliva contains various proteins, nitrogenous products, electrolytes, and so on, which could influence the antivirus effect of tea. Here, we assessed whether tea inactivated the SARS-CoV-2 which was added in human saliva. A virus was added in healthy human saliva in vitro, and after treatment with black tea or green tea, the infectivity of the virus was evaluated by TCID50 assays. The virus titer fell below the detectable level or less than 1/100 after treatment with black tea or green tea for 10 s. The black tea-treated virus less remarkably replicated in cells compared with the untreated virus. These findings suggest the possibility that the ingestion of tea may inactivate SARS-CoV-2 in saliva in infected individuals, although clinical studies are required to determine the intensity and duration of the anti-viral effect of tea in saliva in humans.

Significant Inactivation of SARS-CoV-2 In Vitro by a Green Tea Catechin, a Catechin-Derivative, and Black Tea Galloylated Theaflavins.

Potential effects of tea and its constituents on SARS-CoV-2 infection were assessed in vitro. Infectivity of SARS-CoV-2 was decreased to 1/100 to undetectable levels after a treatment with black tea, green tea, roasted green tea, or oolong tea for 1 min. An addition of (-) epigallocatechin gallate (EGCG) significantly inactivated SARS-CoV-2, while the same concentration of theasinensin A (TSA) and galloylated theaflavins including theaflavin 3,3'-di-O-gallate (TFDG) had more remarkable anti-viral activities. EGCG, TSA, and TFDG at 1 mM, 40 µM, and 60 µM, respectively, which are comparable to the concentrations of these compounds in tea beverages, significantly reduced infectivity of the virus, viral RNA replication in cells, and secondary virus production from the cells. EGCG, TSA, and TFDG significantly inhibited interaction between recombinant ACE2 and RBD of S protein. These results suggest potential usefulness of tea in prevention of person-to-person transmission of the novel coronavirus.