Potential of green tea EGCG in neutralizing SARS-CoV-2 Omicron variant with greater tropism toward the upper respiratory tract

BACKGROUND: COVID-19 due to SARS-CoV-2 infection has had an enormous adverse impact on global public health. As the COVID-19 pandemic evolves, the WHO declared several variants of concern (VOCs), including Alpha, Beta, Gamma, Delta, and Omicron. Compared with earlier variants, Omicron, now a dominant lineage, exhibits characteristics of enhanced transmissibility, tropism shift toward the upper respiratory tract, and attenuated disease severity. The robust transmission of Omicron despite attenuated disease severity still poses a great challenge for pandemic control. Under this circumstance, its tropism shift may be utilized for discovering effective preventive approaches. SCOPE AND APPROACH: This review aims to estimate the potential of green tea epigallocatechin gallate (EGCG), the most potent antiviral catechin, in neutralizing SARS-CoV-2 Omicron variant, based on current knowledge concerning EGCG distribution in tissues and Omicron tropism. KEY FINDINGS AND CONCLUSIONS: EGCG has a low bioavailability. Plasma EGCG levels are in the range of submicromolar concentrations following green tea drinking, or reach at most low μM concentrations after pharmacological intervention. Nonetheless, its levels in the upper respiratory tract could reach concentrations as high as tens or even hundreds of μM following green tea consumption or pharmacological intervention. An approach for delivering sufficiently high concentrations of EGCG in the pharynx has been developed. Convincing data have demonstrated that EGCG at tens to hundreds of μM can dramatically neutralize SARS-CoV-2 and effectively eliminate SARS-CoV-2-induced cytopathic effects and plaque formation. Thus, EGCG, which exhibits hyperaccumulation in the upper respiratory tract, deserves closer investigation as an antiviral in the current global battle against COVID-19, given Omicron's greater tropism toward the upper respiratory tract.