Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2in vitroinfection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19

The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2in vitroinfection: brequinar, abiraterone acetate, neomycin, and the extract ofHedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin andHedera helixextract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2in vitroinfection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection.