ArticlePLoS pathogens2021
Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Configurationally Locked Ridaifen-B Analogs as Potent Ebola Virus Entry Inhibitors.Journal of medicinal chemistry · 2026Article
- From Diarylsulfides to Diarylamines: New Ebola Virus Entry Inhibitors with Improved Metabolic Stability.Journal of medicinal chemistry · 2025Article
- Guardians at the Gate: Optimization of Small Molecule Entry Inhibitors of Ebola and Marburg Viruses.Journal of medicinal chemistry · 2025Article
- Discovery of Thiophene Derivatives as Potent, Orally Bioavailable, and Blood-Brain Barrier-Permeable Ebola Virus Entry Inhibitors.Journal of medicinal chemistry · 2024Article
- Lipid Selectivity of Membrane Action of the Fragments of Fusion Peptides of Marburg and Ebola Viruses.International journal of molecular sciences · 2024Article
- N-Substituted Pyrrole-Based Heterocycles as Broad-Spectrum Filoviral Entry Inhibitors.Journal of medicinal chemistry · 2024Article
- VLP-based model for the study of airborne viral pathogens.Microbiology spectrum · 2024Article
- A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus.eLife · 2024Article
- VLP-Based Model for Study of Airborne Viral Pathogens.bioRxiv : the preprint server for biology · 2024Article
- Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline.Frontiers in microbiology · 2024Review
- Antiviral PROTACs: Opportunity borne with challenge.Cell insight · 2023Review
- Sub-cellular sequestration of alkaline drugs in lysosomes: new insights for pharmaceutical development of lysosomal fluid.Research in pharmaceutical sciences · 2023Article
- Comparative analyses of small molecule and antibody inhibition on glycoprotein-mediated entry of Měnglà virus with other filoviruses.Journal of medical virology · 2022Article
- Evaluation of Phenol-Substituted Diphyllin Derivatives as Selective Antagonists for Ebola Virus Entry.ACS infectious diseases · 2022Article
- Ebola Entry Inhibitors Discovered fromInternational journal of molecular sciences · 2022Article
- Ebola Virus Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Peptide-Based Vaccines and Therapeutics for COVID-19.International journal of peptide research and therapeutics · 2022Review
- Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.mBio · 2021Review
- SARS-CoV-2 cell entry and targeted antiviral development.Acta pharmaceutica Sinica. B · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Many small molecules have been identified as entry inhibitors of filoviruses. However, a lack of understanding of the mechanism of action for these molecules limits further their development as anti-filoviral agents. Here we provide evidence that toremifene and other small molecule entry inhibitors have at least three distinctive mechanisms of action and lay the groundwork for future development of anti-filoviral agents. The three mechanisms identified here include: (1) direct binding to the internal fusion loop region of Ebola virus glycoprotein (GP); (2) the HR2 domain is likely the main binding site for Marburg virus GP inhibitors and a secondary binding site for some EBOV GP inhibitors; (3) lysosome trapping of GP inhibitors increases drug exposure in the lysosome and further improves the viral inhibition. Importantly, small molecules targeting different domains on GP are synergistic in inhibiting EBOV entry suggesting these two mechanisms of action are distinct. Our findings provide important mechanistic insights into filovirus entry and rational drug design for future antiviral development.
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What OpenQuestion holds
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.