ArticleJournal of virology2019
Identification of Clotrimazole Derivatives as Specific Inhibitors of Arenavirus Fusion.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial.Acta anaesthesiologica Scandinavica · 2022Trial
- The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides.Biology of the cell · 2025Review
- Targeting n-myristoyltransferases promotes a pan-Mammarenavirus inhibition through the degradation of the Z matrix protein.PLoS pathogens · 2024Article
- Article
- Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis.Scientific reports · 2024Article
- Treatment of highly virulent mammarenavirus infections-status quo and future directions.Expert opinion on drug discovery · 2024Review
- Entry inhibitors as arenavirus antivirals.Frontiers in microbiology · 2024Review
- Article
- The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.Nature biotechnology · 2022Article
- Estimation of virus-mediated cell fusion rate of SARS-CoV-2.Virology · 2022Article
- Lassa virus glycoprotein complex review: insights into its unique fusion machinery.Bioscience reports · 2022Review
- Inhibition of Arenavirus Entry and Replication by the Cell-Intrinsic Restriction Factor ZMPSTE24 Is Enhanced by IFITM Antiviral Activity.Frontiers in microbiology · 2022Article
- Article
- Progress in Anti-Mammarenavirus Drug Development.Viruses · 2021Review
- Article
- Interplay between RNA Viruses and Promyelocytic Leukemia Nuclear Bodies.Veterinary sciences · 2021Review
- Inhibition of Arenaviruses by Combinations of Orally Available Approved Drugs.Antimicrobial agents and chemotherapy · 2021Article
- Article
- A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.PLoS neglected tropical diseases · 2020Article
- Validation and clinical evaluation of a SARS-CoV-2 surrogate virus neutralisation test (sVNT).Emerging microbes & infections · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arenaviruses are a large family of emerging enveloped negative-strand RNA viruses that include several causative agents of viral hemorrhagic fevers. For cell entry, human-pathogenic arenaviruses use different cellular receptors and endocytic pathways that converge at the level of acidified late endosomes, where the viral envelope glycoprotein mediates membrane fusion. Inhibitors of arenavirus entry hold promise for therapeutic antiviral intervention and the identification of "druggable" targets is of high priority. Using a recombinant vesicular stomatitis virus pseudotype platform, we identified the clotrimazole-derivative TRAM-34, a highly selective antagonist of the calcium-activated potassium channel KCa3.1, as a specific entry inhibitor for arenaviruses. TRAM-34 specifically blocked entry of most arenaviruses, including hemorrhagic fever viruses, but not Lassa virus and other enveloped viruses. Anti-arenaviral activity was likewise observed with the parental compound clotrimazole and the derivative senicapoc, whereas structurally unrelated KCa3.1 inhibitors showed no antiviral effect. Deletion of KCa3.1 by CRISPR/Cas9 technology did not affect the antiarenaviral effect of TRAM-34, indicating that the observed antiviral effect of clotrimazoles was independent of the known pharmacological target. The drug affected neither virus-cell attachment, nor endocytosis, suggesting an effect on later entry steps. Employing a quantitative cell-cell fusion assay that bypasses endocytosis, we demonstrate that TRAM-34 specifically inhibits arenavirus-mediated membrane fusion. In sum, we uncover a novel antiarenaviral action of clotrimazoles that currently undergo
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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.