ArticleProceedings of the National Academy of Sciences of the United States of America2010
Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
80 citing papers in PubMed, 154 citations in OpenAlex.
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- Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism.Molecules (Basel, Switzerland) · 2023Article
- Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.Current issues in molecular biology · 2023Review
- Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs.Antiviral research · 2023Article
- The Degree of Hydroxylation of Phenolic Rings Determines the Ability of Flavonoids and Stilbenes to Inhibit Calcium-Mediated Membrane Fusion.Nutrients · 2023Article
- Nucleoside Analogs and Perylene Derivatives Modulate Phase Separation of SARS-CoV-2 N Protein and Genomic RNA In Vitro.International journal of molecular sciences · 2022Article
- Lipid and Lipidation in Membrane Fusion.The Journal of membrane biology · 2022Review
- Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses.Biomolecules · 2022Article
- On the Sensitivity of the Virion Envelope to Lipid Peroxidation.Microbiology spectrum · 2022Article
- Chromone-Containing Allylmorpholines Influence Ion Channels in Lipid Membranes via Dipole Potential and Packing Stress.International journal of molecular sciences · 2022Article
- Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo.Pharmaceuticals (Basel, Switzerland) · 2022Article
- New Derivatives of 5-Substituted Uracils: Potential Agents with a Wide Spectrum of Biological Activity.Molecules (Basel, Switzerland) · 2022Article
- Broad-spectrum Respiratory Virus Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022Article
- Photosensitizing Antivirals.Molecules (Basel, Switzerland) · 2021Review
- Active Components fromInternational journal of molecular sciences · 2021Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Antiviral drugs targeting viral proteins often result in prompt selection for resistance. Moreover, the number of viral targets is limited. Novel antiviral targets are therefore needed. The unique characteristics of fusion between virion envelopes and cell membranes may provide such targets. Like all fusing bilayers, viral envelopes locally adopt hourglass-shaped stalks during the initial stages of fusion, a process that requires local negative membrane curvature. Unlike cellular vesicles, however, viral envelopes do not redistribute lipids between leaflets, can only use the energy released by virion proteins, and fuse to the extracellular leaflets of cell membranes. Enrichment in phospholipids with hydrophilic heads larger than their hydrophobic tails in the convex outer leaflet of vesicles favors positive curvature, therefore increasing the activation energy barrier for fusion. Such phospholipids can increase the activation barrier beyond the energy provided by virion proteins, thereby inhibiting viral fusion. However, phospholipids are not pharmacologically useful. We show here that a family of synthetic rigid amphiphiles of shape similar to such phospholipids, RAFIs (rigid amphipathic fusion inhibitors), inhibit the infectivity of several otherwise unrelated enveloped viruses, including hepatitis C and HSV-1 and -2 (lowest apparent IC(50) 48 nM), with no cytotoxic or cytostatic effects (selectivity index > 3,000) by inhibiting the increased negative curvature required for the initial stages of fusion.
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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.