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

ABSTRACT: COVID-19 is a disease with unique characteristics that include lung thrombosis¹, frequent diarrhoea², abnormal activation of the inflammatory response³ and rapid deterioration of lung function consistent with alveolar oedema⁴. 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 syncytia. We converged on the ide

SUBMITTER: Braga L 

PROVIDER: S-EPMC7611055 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature