COVID-19 preclinical drug development database
Name: Mauro Giacca
Email Address: email@example.com
Phone Number: +44 207 848 1309
Professor Mauro Giacca Professor Juan Burrone Professor Ajay Shah Professor Wendy Barclay (Imperial College London)
COVID-19 is a unique disease with distinctive clinical characteristics, including extensive thrombosis, frequent diarrhoea and hyperinflammation, in addition to unexplained symptomatology. The pathological substrates for these characteristics remain largely elusive. We found that the lungs of patients with COVID-19 show the presence of infected pneumocytes with abnormal morphological characteristics and frequent multinucleation, a feature that depends on the presence of the viral Spike protein on the plasma membrane of the infected cells. Based on this information, we performed two high-content microscopy, high-throughput screenings with over ~3000 small molecules to search for approved drugs that inhibit Spike-driven syncytia formation. The two screenings converged on the identification of 83 drugs that markedly inhibited Spike-mediate cell-cell fusion, several of which belonged to defined pharmacological classes. After testing the effects of these drugs on infectious SARS-CoV-2, we focussed our attention on three drugs that were among the most effective at inhibiting Spike-induce syncytia and protecting the cells against virus-induced death.