Epigallocatechin gallate inhibits rabies virus glycoprotein‑mediated infection in vitro

Rabies is one of the most lethal zoonotic disease and causes approximately 60,000 human deaths annually. The high cost of immunoglobulin prophylaxis and the need for cold chain maintenance highlight the need for accessible antiviral strategies, particularly in resource-limited settings. Epigallocatechin gallate (EGCG), the major polyphenolic compound of Camellia sinensis, has broad-spectrum antiviral activity. We therefore investigated its activity against Rabies virus (RABV). Because RABV requires BSL-3 containment, we first used a recombinant Vesicular Stomatitis Virus pseudotyped with RABV glycoprotein (pRABV) as a surrogate. EGCG inhibited pRABV infection in a concentration-dependent manner, with an EC₅₀ of approximately 0.15 µg/mL and a selectivity index > 551.72. Time-of-addition, attachment, and entry assays showed that EGCG reduced pRABV infectivity when present during viral adsorption or after pre-incubation with viral particles, whereas no inhibition was observed when cells were treated before infection or after virus internalization. Viral infectivity remained almost completely abolished in a virucidal assay even after EGCG was diluted below its effective antiviral concentration, supporting a direct and irreversible effect on viral particles. EGCG activity was further confirmed using authentic RABV and disease-relevant cell types, including myotubes and neurons. Overall, these findings indicate that EGCG inhibits early stages of the RABV replication cycle, primarily by interfering with viral attachment and directly affecting viral particles. Further studies are needed to define the molecular basis of this interaction and assess the therapeutic potential of EGCG against RABV.