ArticleProtein science : a publication of the Protein Society2015
Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.Pathogens (Basel, Switzerland) · 2025Review
- Research strategies of the N-peptide fusion inhibitor: a promising direction for discovering novel antivirals.Journal of virology · 2025Review
- Selective Activation of Peptide-Thioester Precursors for Templated Native Chemical Ligations.Angewandte Chemie (International ed. in English) · 2025Article
- Structure and Function of the SARS-CoV-2 6-HB Fusion Core and Peptide-based Fusion Inhibitors: A Review.Current medicinal chemistry · 2025Review
- Improved Handling of Peptide Segments Using Side Chain-Based "Helping Hand" Solubilizing Tools.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Traceless Click-Assisted Native Chemical Ligation Enabled by Protecting Dibenzocyclooctyne from Acid-Mediated Rearrangement with Copper(I).Bioconjugate chemistry · 2021Article
- Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry.Journal of virology · 2019Article
- Role of the Ebola membrane in the protection conferred by the three-mAb cocktail MIL77.Scientific reports · 2018Article
- Triterpenoids manipulate a broad range of virus-host fusion via wrapping the HR2 domain prevalent in viral envelopes.Science advances · 2018Article
- Aligator: A computational tool for optimizing total chemical synthesis of large proteins.Bioorganic & medicinal chemistry · 2017Review
- Article
- Designing helical peptide inhibitors of protein-protein interactions.Current opinion in structural biology · 2016Review
- Protein Science best paper awards to Tracy Clinton and Michael Thompson.Protein science : a publication of the Protein Society · 2016Article
- An effective strategy for recapitulating N-terminal heptad repeat trimers in enveloped virus surface glycoproteins for therapeutic applications.Chemical science · 2016Article
- Protein engineering in the 21st century.Protein science : a publication of the Protein Society · 2015Article
- Chemical and Structural Aspects of Ebola Virus Entry Inhibitors.ACS infectious diseases · 2015Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify D-peptide inhibitors of ebolavirus entry.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.