Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation [article]

Angela Serra, Michele Fratello, Antonio Federico, Ravi Ojha, Riccardo Provenzani, Ervin Tasnadi, Luca Cattelani, Giusy del Giudice, Pia Anneli Sofia Kinaret, Laura Aliisa Saarimaki, Alisa Pavel, Vincenzo Cerullo (+6 others)
2021 bioRxiv   pre-print
New affordable therapeutic protocols for COVID-19 are urgently needed despite the increasing number of effective vaccines and monoclonal antibodies. To this end, there is increasing attention towards computational methods for drug repositioning and de novo drug design. Here, we systematically integrated multiple data-driven computational approaches to perform virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the set of prioritized drugs, we selected a subset
more » ... representative candidates to test in human cells. Two compounds, 7-hydroxystaurosporine and bafetinib, showed synergistic antiviral effects in our in vitro experiments, and strongly inhibited viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, we extracted and prioritized the chemical substructures of the identified drugs, providing a chemical vocabulary that may help to design new effective drugs.
doi:10.1101/2021.04.15.440004 fatcat:jvpshosxgvg4je7ioaatg2um4m