ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus, is a major global health challenge, as there is no efficient treatment for the moderate to severe disease. ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host, hence we assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients. Interestingly, rucaparib, unlike other PARP inhibitors, reduced SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein-induced overexpression of IL-6, a key cytokine in COVID-19, was inhibited by rucaparib at pharmacologically relevant concentrations. These findings build a case for repurposing rucaparib for treating COVID-19 disease.
