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Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia

Nature. 2021-04; 
Luca Braga, Hashim Ali, Ilaria Secco, Elena Chiavacci, Guilherme Neves, Daniel Goldhill, Rebecca Penn, Jose M Jimenez-Guardeño, Ana M Ortega-Prieto, Rossana Bussani, Antonio Cannatà, Giorgia Rizzari, Chiara Collesi, Edoardo Schneider, Daniele Arosio, Ajay M Shah, Wendy S Barclay, Michael H Malim, Juan Burrone, Mauro Giacca
Products/Services Used Details Operation
Custom Vector Construction The following expression vectors were used: hTMEM16A (GenScript OHu26085D), hTMEM16F (GenScript OHu26351D) Get A Quote

摘要

COVID-19 is a disease with unique characteristics that include lung thrombosis, frequent diarrhoea, abnormal activation of the inflammatory response and rapid deterioration of lung function consistent with alveolar oedema. The pathological substrate for these findings remains unknown. Here we show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation. The generation of these syncytia results from activation of the SARS-CoV-2 spike protein at the cell plasma membrane level. On the basis of these observations, we performed two high-content microscopy-based screenings with more than 3,000 approved drugs to search for inhibitors of spike-driven s... More

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