Phenotypic Prioritization of Diphyllin Derivatives That Block Filoviral Cell Entry by Vacuolar (H⁺ )-ATPase Inhibition.

ABSTRACT: Many viruses use endosomal pathways to gain entry into cells and propagate infection. Sensing of endosomal acidification is a trigger for the release of many virus cores into the cell cytosol. Previous efforts with inhibitors of vacuolar ATPase have been shown to block endosomal acidification and affect viral entry, albeit with limited potential for therapeutic selectivity. In this study, four novel series of derivatives of the vacuolar ATPase inhibitor diphyllin were synthesized to assess their potential for enhancing potency and anti-filoviral activity over cytotoxicity. Derivatives that suitably blocked cellular entry of Ebola pseudotyped virus were further evaluated as inhibitors of endosomal acidification and isolated human vacuolar ATPase activity. Several compounds with significant

SUBMITTER: Lindstrom A 

PROVIDER: S-EPMC6387451 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature