Repurposing FDA-Approved Drugs for Treatment of 2019-nCoV-induced Disease

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. A novel coronavirus (SARS-CoV-2) originating in Wuhan, China has reached pandemic status and causes a disease termed COVID-19. Therapeutics and vaccines are urgently needed. The normal pace of new drug development is incompatible with strategies to rapidly combat COVID-19. Drug combinations with antiviral and anti-inflammatory activity will likely be essential to treat infected patients, as acute respiratory virus-induced disease is commonly mediated by inflammatory responses to infection. An alternative strategy to rapidly identify therapeutics to combat SARS-CoV-2 is drug repurposing. As the drugs are already FDA-approved, it is cost-effective and time-efficient. To this end, we will exploit MuSIC (multiplex screening of interacting compounds) screening of a unique library consisting of ~1,000 drugs to identify single and synergistic interacting compounds that have either SARS-CoV-2 antiviral activity or anti-inflammatory activities, with limited/no toxicities. This library includes FDA-approved compounds and antiviral drugs that showed activity against other cornoviruses (SARS-CoV & MERS-CoV) (1). Drug candidates will be validated using SARS-CoV-2-infection of well-differentiated primary human airway epithelial cell cultures (WD-PAECs), which are excellent surrogates of human airway epithelium. WD-PAECs represent the most relevant pre-clinical translational model for screening therapeutic drugs for COVID-19. SARS-CoV-2 uses that same receptor/entry factors as SARS-CoV (2), which infects WD-PAEC cultures. Our findings will identify candidate drugs for treating COVID-19 patients, which can quickly enter clinical trials or be employed for compassionate use, especially in the case of viral diseases lacking specific treatments. (1): Mani et al. J Young Pharm, 2019; 11(2) : 117-121 (2): Hoffmann et al. bioRxiv https: