ArticleJournal of the American Chemical Society2020
Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers.
Article in Journal of the American Chemical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 44 citations in OpenAlex.
- Supramolecular Polymer-Surfactant Co-Assemblies for Multivalent HSV-1 Inhibition.Angewandte Chemie (International ed. in English) · 2026Article
- Broad-Spectrum Antiviral and Antibacterial Activity of the Scorpion Venom Peptide HP1090.Toxins · 2026Article
- Identification and Characterization of an In Silico Designed Membrane-Active Peptide with Antiviral Properties.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- Advanced Molecular Tweezers Effectively Target Membranes Lacking Choline Headgroups for Broad-Spectrum Antiviral Efficacy.Journal of the American Chemical Society · 2026Article
- Self-assembled nanosheets of biocompatible polymers as universal cell-membrane mimic to block viral infection.Bioactive materials · 2025Article
- Membrane-Targeting Antivirals.International journal of molecular sciences · 2025Review
- Molecular Tweezers for Biomimetic Recognition of Carbohydrates.Chembiochem : a European journal of chemical biology · 2025Review
- Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens.Nature microbiology · 2024Article
- Review
- Molecular Machines For The Control Of Transmembrane Transport.Journal of the American Chemical Society · 2023Review
- Lipid-Centric Approaches in Combating Infectious Diseases: Antibacterials, Antifungals and Antivirals with Lipid-Associated Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2023Review
- Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases.Journal of controlled release : official journal of the Controlled Release Society · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM) · 2023Review
- Tailored lipopeptide surfactants as potentially effective drugs to treat SARS-CoV-2 infection.Medical hypotheses · 2022Article
- Advanced Molecular Tweezers with Lipid Anchors against SARS-CoV-2 and Other Respiratory Viruses.JACS Au · 2022Article
- Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Phosphorylation of covalent organic framework nanospheres for inhibition of amyloid-β peptide fibrillation.Chemical science · 2022Article
- The bacteriocin Angicin interferes with bacterial membrane integrity through interaction with the mannose phosphotransferase system.Frontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
32 authors at 6 institutions in 2 countries.
Funding
Abstract
Broad-spectrum antivirals are powerful weapons against dangerous viruses where no specific therapy exists, as in the case of the ongoing SARS-CoV-2 pandemic. We discovered that a lysine- and arginine-specific supramolecular ligand (CLR01) destroys enveloped viruses, including HIV, Ebola, and Zika virus, and remodels amyloid fibrils in semen that promote viral infection. Yet, it is unknown how CLR01 exerts these two distinct therapeutic activities. Here, we delineate a novel mechanism of antiviral activity by studying the activity of tweezer variants: the "phosphate tweezer" CLR01, a "carboxylate tweezer" CLR05, and a "phosphate clip" PC. Lysine complexation inside the tweezer cavity is needed to antagonize amyloidogenesis and is only achieved by CLR01. Importantly, CLR01 and CLR05 but not PC form closed inclusion complexes with lipid head groups of viral membranes, thereby altering lipid orientation and increasing surface tension. This process disrupts viral envelopes and diminishes infectivity but leaves cellular membranes intact. Consequently, CLR01 and CLR05 display broad antiviral activity against all enveloped viruses tested, including herpesviruses, Measles virus, influenza, and SARS-CoV-2. Based on our mechanistic insights, we potentiated the antiviral, membrane-disrupting activity of CLR01 by introducing aliphatic ester arms into each phosphate group to act as lipid anchors that promote membrane targeting. The most potent ester modifications harbored unbranched C4 units, which engendered tweezers that were approximately one order of magnitude more effective than CLR01 and nontoxic. Thus, we establish the mechanistic basis of viral envelope disruption by specific tweezers and establish a new class of potential broad-spectrum antivirals with enhanced activity.
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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.