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

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
DOI: 10.3390/v10040201 Publication Date: 2018-04-18T07:51:13Z
ABSTRACT
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.
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