ArticleFrontiers in cardiovascular medicine2022
SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet procoagulant activity.
Article in Frontiers in cardiovascular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Recent advances in TMEM16F: structural plasticity, functional versatility, and implications for human diseases.Cell communication and signaling : CCS · 2026Review
- Calcium dependent activation of the TMEM16F scramblase and ion channel.Nature structural & molecular biology · 2026Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.Pathogens (Basel, Switzerland) · 2024Review
- In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- TMEM16 proteins: CaInternational journal of molecular medicine · 2024Review
- The Dual-Targeted Fusion Inhibitor Clofazimine Binds to the S2 Segment of the SARS-CoV-2 Spike Protein.Viruses · 2024Article
- Niclosamide, but not ivermectin, inhibits anoctamin 1 and 6 and attenuates inflammation of the respiratory tract.Pflugers Archiv : European journal of physiology · 2024Article
- The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19.International journal of molecular sciences · 2023Review
- SARS-CoV-2 infection boosts inflammation in atherosclerotic plaques.Nature cardiovascular research · 2023Article
- SARS-CoV-2 Syncytium under the Radar: Molecular Insights of the Spike-Induced Syncytia and Potential Strategies to Limit SARS-CoV-2 Replication.Journal of clinical medicine · 2023Review
- Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombosis of the lung microvasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis that is endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting Spike-induced TMEM16 activation. As TMEM16F plays an important role in stimulating the procoagulant activity of platelets, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Here we show that Spike, present either on the virion envelope or on the cell plasma membrane, promotes platelet activation, adhesion and spreading. Spike was active as a sole agonist or, even more effectively, by enhancing the function of known platelet activators. In particular, Spike-induced a marked procoagulant phenotype in platelets, by enhancing Ca
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