Comparative Antiviral Efficacy Of Different Autophagy Inhibitors Against Covid-19

As of May 10, 2020, worldwide, over 4.15 million people have been diagnosed and over 282,000 deaths with ongoing deadly coronavirus disease-19 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Currently, there are no approved treatments against COVID-19. Vaccines are under development, but they will be available at least in one year. We need to find quickly new drug targets by fueling basic research projects on SARS- CoV-2 infectivity. A fast track approach would be to reuse already approved drugs that have been broadly tested through multiple clinical trials. Virophagy is a catabolic autophagic pathway used by mammalian cells to destroy viruses. Viruses have now acquired the capability to repurpose autophagy (block or activate) for their lifecycle and pathogenesis. Coronaviruses hijack and fine tune multiple steps of virophagy to escape destruction, increase replication and release from infected cells. Autophagy inhibitors and old anti-malarial drugs, Chloroquine (CQ) and Hydroxychloroquine (HCQ) are creating a lot of excitement in the fight against COVID-19. However, clinical data on CQ and HCQ against COVID-19 is still very limited and inconclusive. At the basic research level, our CIAO-COVID-19 project will investigate the impact of different druggable steps of autophagy on SARS-CoV-2 pseudovirus entry into human airway epithelial cells. At the clinical level, this study aims to compare antiviral efficacy of different potent, selective and specific autophagy inhibitors against COVID-19 infection in vitro. We believe that the knowledge generated during this project will provide important clues for the control and treatment of COVID-19.