ArticleNature2016
Toremifene interacts with and destabilizes the Ebola virus glycoprotein.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
What it found
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Who cites it
160 citing papers in PubMed, 250 citations in OpenAlex.
- Differential glycosylation in the envelope glycoprotein enhances DC-SIGN-mediated cell entry of the West African Ebolavirus Makona.Emerging microbes & infections · 2026Article
- A small molecule inhibits Ebola virus entry through glycoprotein stabilization.Nature communications · 2026Article
- Deadbolt Drug Discovery: Locking the Door to Class 1 Viral Entry by Small Molecules.ACS infectious diseases · 2026Review
- Configurationally Locked Ridaifen-B Analogs as Potent Ebola Virus Entry Inhibitors.Journal of medicinal chemistry · 2026Article
- Pan-Ebolavirus nanoparticle vaccine provides protection in rodents from lethal infection by Zaire and Sudan viruses.Nature communications · 2026Article
- Article
- Review
- QSAR-Guided and Fragment-Based Drug Design of Monoterpenoid Inhibitors Targeting Ebola Virus Glycoprotein.International journal of molecular sciences · 2026Article
- A highly potent nanobody-based bispecific therapeutic provides broad-spectrum protection against ebolavirus.Nature communications · 2026Article
- Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.Pathogens (Basel, Switzerland) · 2025Review
- Rational design of next-generation filovirus vaccines combining glycoprotein stabilization and nanoparticle display with glycan modification.Nature communications · 2025Article
- Drug repositioning as a promising approach for the eradication of emerging and re-emerging viral agents.Molecular diversity · 2025Review
- Conserved Filovirus Proteins as Targets of Broad-Spectrum Antivirals.bioRxiv : the preprint server for biology · 2025Article
- Rational design of next-generation filovirus vaccines through glycoprotein stabilization, nanoparticle display, and glycan modification.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Use of Viral Vectors Pseudotyped with Viral Glycoproteins as Tools to Study Antibody-Mediated Neutralizing Activity.Microorganisms · 2025Review
- Influenza a Virus Inhibition: Evaluating Computationally Identified Cyproheptadine Through In Vitro Assessment.International journal of molecular sciences · 2025Article
- The Role of Glycans in Human Immunity-A Sweet Code.Molecules (Basel, Switzerland) · 2025Review
- From Diarylsulfides to Diarylamines: New Ebola Virus Entry Inhibitors with Improved Metabolic Stability.Journal of medicinal chemistry · 2025Article
- Molecular basis for the increased fusion activity of the Ebola virus glycoprotein epidemic variant A82V: Insights from simulations and experiments.Cell reports · 2025Article
- The Lassa Virus Stable Signal Peptide Undergoes a Conformational Change to Aid Viral Fusion.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ebola viruses (EBOVs) are responsible for repeated outbreaks of fatal infections, including the recent deadly epidemic in West Africa. There are currently no approved therapeutic drugs or vaccines for the disease. EBOV has a membrane envelope decorated by trimers of a glycoprotein (GP, cleaved by furin to form GP1 and GP2 subunits), which is solely responsible for host cell attachment, endosomal entry and membrane fusion. GP is thus a primary target for the development of antiviral drugs. Here we report the first, to our knowledge, unliganded structure of EBOV GP, and high-resolution complexes of GP with the anticancer drug toremifene and the painkiller ibuprofen. The high-resolution apo structure gives a more complete and accurate picture of the molecule, and allows conformational changes introduced by antibody and receptor binding to be deciphered. Unexpectedly, both toremifene and ibuprofen bind in a cavity between the attachment (GP1) and fusion (GP2) subunits at the entrance to a large tunnel that links with equivalent tunnels from the other monomers of the trimer at the three-fold axis. Protein–drug interactions with both GP1 and GP2 are predominately hydrophobic. Residues lining the binding site are highly conserved among filoviruses except Marburg virus (MARV), suggesting that MARV may not bind these drugs. Thermal shift assays show up to a 14 °C decrease in the protein melting temperature after toremifene binding, while ibuprofen has only a marginal effect and is a less potent inhibitor. These results suggest that inhibitor binding destabilizes GP and triggers premature release of GP2, thereby preventing fusion between the viral and endosome membranes. Thus, these complex structures reveal the mechanism of inhibition and may guide the development of more powerful anti-EBOV drugs.
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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.