ArticleCommunications biology2021
Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 66 citations in OpenAlex.
- Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.European journal of neurology · 2024Trial
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.Molecular biology and evolution · 2025Article
- Activity and cellular distribution of ORF3a mutants of SARS-CoV-2 variants of concern.The Journal of general virology · 2025Article
- Screening bacterial effectors and human virus proteins in yeast to identify host factors driving tombusvirus RNA recombination: a role for autophagy and membrane phospholipid content.Journal of virology · 2025Article
- The SH protein of mumps virus is a druggable pentameric viroporin.Science advances · 2025Article
- New strategies to enhance the efficiency and precision of drug discovery.Frontiers in pharmacology · 2025Review
- Immuno-epigenetic paradigms in coronavirus infection.Frontiers in immunology · 2025Review
- The 6-kilodalton peptide 1 of the familyFrontiers in microbiology · 2025Review
- Screening and discovery of an antiviral candidate inhibiting the SARS-CoV-2 envelope (2-E) channel.Current research in microbial sciences · 2025Article
- Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms.International journal of molecular sciences · 2024Review
- SARS-CoV-2 ORF 3a-mediated currents are inhibited by antiarrhythmic drugs.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Oligomeric State and Drug Binding of the SARS-CoV-2 Envelope Protein Are Sensitive to the Ectodomain.Journal of the American Chemical Society · 2024Article
- Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide.Journal of virology · 2024Article
- SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.Nature communications · 2024Article
- Review
- Thermodynamic and Kinetic Characteristics of Molnupiravir Tautomers and Its Complexes with RNA Purine Bases as an Explanation of the Possible Mechanism of Action of This Novel Antiviral Medicine: A Quantum-Chemical Study.The Journal of organic chemistry · 2023Article
- Hexamethylene amiloride binds the SARS-CoV-2 envelope protein at the protein-lipid interface.Protein science : a publication of the Protein Society · 2023Article
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- Review
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Authors and funding
12 authors at 4 institutions in 4 countries.
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Abstract
The dire need for COVID-19 treatments has inspired strategies of repurposing approved drugs. Amantadine has been suggested as a candidate, and cellular as well as clinical studies have indicated beneficial effects of this drug. We demonstrate that amantadine and hexamethylene-amiloride (HMA), but not rimantadine, block the ion channel activity of Protein E from SARS-CoV-2, a conserved viroporin among coronaviruses. These findings agree with their binding to Protein E as evaluated by solution NMR and molecular dynamics simulations. Moreover, we identify two novel viroporins of SARS-CoV-2; ORF7b and ORF10, by showing ion channel activity in a X. laevis oocyte expression system. Notably, amantadine also blocks the ion channel activity of ORF10, thereby providing two ion channel targets in SARS-CoV-2 for amantadine treatment in COVID-19 patients. A screen of known viroporin inhibitors on Protein E, ORF7b, ORF10 and Protein 3a from SARS-CoV-2 revealed inhibition of Protein E and ORF7b by emodin and xanthene, the latter also blocking Protein 3a. This illustrates a general potential of well-known ion channel blockers against SARS-CoV-2 and specifically a dual molecular basis for the promising effects of amantadine in COVID-19 treatment. We therefore propose amantadine as a novel, cheap, readily available and effective way to treat COVID-19.
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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.