Protein Phosphatase 1-Targeting Small-Molecule C31 Inhibits Ebola Virus Replication.

ABSTRACT:

Background

Ebola virus (EBOV) infection causes severe hemorrhagic fever. EBOV transcription is controlled by host protein phosphatase 1 (PP1), which dephosphorylates VP30 protein. We previously developed 1E7-03, a compound targeting a noncatalytic site of PP1 that induced VP30 phosphorylation and inhibited EBOV transcription. Here, we attempted to further improve 1E7-03, which was not stable in murine serum.

Results

High-throughput screening with EBOV-green fluorescent protein was conducted on 72 1E7-03 analogs and identified 6 best inhibitory and the least toxic compounds. A parallel in silico screening of compounds from the ZINC database by docking to PP1 identified the best-binding compound C31, which was also present among the top 6 compounds found in the viral screen. C

SUBMITTER: Ammosova T 

PROVIDER: S-EPMC6249606 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature