Repurposing approved drugs as potent antiviral combinations to treat COVID-19 disease

SARS-CoV-2 is responsible for the worldwide pandemic that has devasted most countries since it emerged in December 2019. Huge efforts have been made to generate vaccines and drugs to prevent and treat infection, respectively. Vaccine development has proceeded at an unprecendent pace and emergency authorisation was given for a number of vaccines in late 2020 and early 2021. Some drugs have also been shown to have therapeutic benefits against severe COVID-19 disease, most of which are immunemodulators. However, there has been very little success with antiviral therapeutics, with the notable exceptions of remdesivir and monoclonal antibody cocktails. This project, therefore, will seek to bridge this gap and seeks to identify novel drug combinations with enhanced antiviral activities against SARS-CoV-2, the causative agent of COVID-19 disease. We have assembled a very strong team of expertis from Queen's University Belfast, University of Liverpool and University of Oxford. We will initially screen a bespoke library of 140 drugs with known antiviral activity against SARS-CoV-2 for combinations that enhance their antiviral potential. The best combinations will then undergo a robust series of in vitro and in vivo protocols to validate their potential. The data will provide the rationale to make strong recommendations to UK-CTAP for progression to clinical trials. In parallel, we will evaluate the propensity of the drug combinations to elicit drug-resistant mutants, which is an important consideration for drugs that will be used on a massive scale globally. Finally, and in parallel, we have identified 2 large drug libraries that have not been subjected yet to combination drug screening. We will exploit our robust drug screening platform of protocols to identify back-up drug combination candidates to ensure a pipeline of antiviral drugs against SARS-CoV-2 for the future.