Antiviral effect of epigallocatechin gallate via impairing Rabies virus attachment to target cell

Rabies leads to approximately 59,000 human deaths annually across vast regions globally, despite the fact that effective preventive strategies have been established to control this disease. Rabies virus is capable of infecting mammals. In up to 99% of human cases, transmission occurs through the bite of domestic dogs. The occurrence of human rabies can be prevented by vaccination, following pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) in individuals who have been bitten by rabid animals. Furthermore, eliminating the source of infection is achievable through continuous mass vaccination of reservoir animal populations. While many industrialized nations have successfully eliminated rabies from their domestic dog populations, in most of the developing countries the disease continues to persist due to inadequate control and virus circulation in domestic dogs. The need for creating novel antiviral substances, particularly ones capable of tackling supply chain and cost-related problems of vaccines, is emphasized by the absence of viable treatments for rabies. Small-molecule antiviral agents are a hopeful avenue due to their economical production and extended shelf life. Although past efforts to find small-molecule inhibitors for rabies have encountered obstacles like cytotoxicity, ongoing research is dedicated to investigating a potential drug candidate. Epigallocatechin-3-O-gallate (EGCG), which is a polyphenolic compound and the major catechin component of green tea, previously has demonstrated remarkable antiviral properties against a broad spectrum of viruses, encompassing both DNA and RNA viruses. Building upon this promising antiviral potential, our study aimed to investigate whether EGCG also exhibits antiviral activity against the rabies virus. To comprehensively assess EGCG's impact on rabies virus infection, we employed a variety of virological assays. These assays included time-of-addition, virucidal, viral entry and attachment assays, utilizing a rabies pseudotyped Vesicular stomatitis-based system on Vero CCL81 cell lines and stem cell-derived neurons. Through these investigations, we observed that EGCG significantly inhibited the pseudovirus infection interfering with the attachment of viral particles to host cells. 4 To validate these findings, experiments using real rabies virus have been conducted by the staff of the National Reference Center for rabies at the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe). The results have been highly promising and hold the potential to further investigate the potential use of EGCG for the treatment of rabies.