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Macrocyclic peptides inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and Karyopherin alpha 5

Abstract

Ebola virus infection leads to severe hemorrhagic fever in human and non-human primate with an average case fatality rate of 50%. To date, numerous potential therapies are in development, but FDA-approved drugs or vaccines are yet unavailable. Ebola viral protein 24 (VP24) is a multifunctional protein that plays critical roles in pathogenesis of Ebola virus infection, e.g. innate immune suppression by blockade the interaction between KPNA and PY-STAT1. Here we report macrocyclic peptides inhibitors of the protein-protein interaction (PPI) of VP24-KPNA5 by means of the RaPID (Random non-standard Peptides Integrated Discovery) system. These macrocyclic peptides showed remarkable high affinity to recombinant Zaire Ebola virus VP24 (eVP24) with the dissociation constant of a single digit nM rang, which could also display successful disruption of for the eVP24-KPNA interaction. This work provided for the first time a chemical probe capable of modulating the PPI interaction and a starting point for the development of unique anti-viral drugs against Ebola virus.

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Publication details

The article was received on 03 Jan 2017, accepted on 03 May 2017 and first published on 17 May 2017


Article type: Paper
DOI: 10.1039/C7OB00012J
Citation: Org. Biomol. Chem., 2017, Accepted Manuscript
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    Macrocyclic peptides inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and Karyopherin alpha 5

    X. Song, L. Lu, T. Passioura and H. Suga, Org. Biomol. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7OB00012J

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