Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry.

ABSTRACT: A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion. Two computational structure-based virtual screens of ∼1.7 M compounds were performed (DOCK program) against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing.

SUBMITTER: Singleton CD 

PROVIDER: S-EPMC6639268 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature