Tea Polyphenols in the COVID-19 Era: Mechanistic Insights and Translational Challenges.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has driven the global COVID-19 pandemic, imposing a tremendous burden on public health. As the virus continually evolves through rapid mutations, the pandemic has transitioned into a prolonged endemic phase. Despite the development of novel drugs and vaccines, clinical outcomes remain suboptimal for vulnerable populations, including the elderly and those with comorbidities or compromised immunity. Tea polyphenols, a class of structurally diverse and bioactive nutraceuticals, may modulate viral entry, replication, and host inflammatory pathways implicated in disease progression through pleiotropic effects on viral attachment, membrane fusion, intracellular replication, and proteolytic processing. Here, we provide an updated chemo-biological perspective on the antiviral and immunomodulatory mechanisms of tea polyphenols against SARS-CoV-2. Current evidence highlights their potential to serve as promising candidates for further mechanistic and translational investigation as adjunctive strategies and nutraceuticals for COVID-19 management. Importantly, no large-scale randomized controlled trials have yet demonstrated clinical benefit of tea polyphenols in COVID-19.