Inhibition of Rabies Virus by 1,2,3,4,6-Penta-O-galloyl-β-d-Glucose Involves mTOR-Dependent Autophagy

• DOI: 10.3390/v10040201
• Publication Date: 2018-04-18T07:51:13Z
• Authors: Zhongzhong Tu; Wenjie Gong; Yan Zhang; Ye Feng; Yan Liu; Changchun Tu
• Keywords: PGG; IPS; RABV; antiviral; CVS-11; 0301 basic medicine; Rabies; IPS; Virus Replication; Microbiology; Antiviral Agents; Article; Mice; 03 medical and health sciences; Autophagy; CVS-11; Animals; 0303 health sciences; PGG; TOR Serine-Threonine Kinases; antiviral; Survival Analysis; QR1-502; Hydrolyzable Tannins; 3. Good health; Disease Models, Animal; RABV; Rabies virus; Sweetening Agents; Female

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.