SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet procoagulant activity.
COVID-19
Clofazimine
Niclosamide
SARS-CoV-2
Spike
TMEM16F
coagulation
platelets
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2022
2022
Historique:
received:
06
08
2022
accepted:
29
11
2022
entrez:
23
1
2023
pubmed:
24
1
2023
medline:
24
1
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 36684586
doi: 10.3389/fcvm.2022.1013262
pmc: PMC9845929
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1013262Informations de copyright
Copyright © 2023 Cappelletto, Allan, Crescente, Schneider, Bussani, Ali, Secco, Vodret, Simeone, Mascaretti, Zacchigna, Warner and Giacca.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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