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

Tatiana Ammosova, Colette A. Pietzsch, Yasemin Saygideǧer, Andrey Ilatovsky, Xionghao Lin, Andrey Ivanov, Namita Kumari, Marina Jerebtsova, Amol Kulkarni, Michael Petukhov, Aykut Üren, Alexander Bukreyev, Sergei Nekhai

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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. C31 showed the best EBOV inhibitory activity among the top 6 compounds and also inhibited EBOV minigenome. C31 bound to the PP1 C-terminal groove in vitro and increased VP30 phosphorylation in cultured cells. C31 demonstrated improved stability in mouse plasma and cell permeability, compared with 1E7-03. It was also detected for 24 hours after injection in mice. Conclusion. C31 represents a novel PP1-targeting EBOV inhibitor with improved pharmacological properties that can be further evaluated for future antifiloviral therapy.

Original languageEnglish (US)
Pages (from-to)S627-S635
JournalJournal of Infectious Diseases
StatePublished - Nov 22 2018


  • Ebola virus
  • protein phosphatase 1
  • transcription inhibitor.

ASJC Scopus subject areas

  • General Medicine


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