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

This project is currently under investigation and is funded by the Medical Research Council (MRC), to support a collaboration between the Queens University Belfast, Centre of Excellence for Long-acting Therapeutics (CELT) and University of Oxford investigators. The project’s aim is to validate a drug screening pipeline platform for rapid but robust progression of drug combinations against Sars-CoV-2 through the pre-clinical pipeline including in vitro analysis, in vivo efficacy studies and pharmacometrics.

Project overview

Since its emergence in 2019, SARS-CoV-2 has had a devastating impact on most countries around the world. There was a global movement to develop vaccines, which worked at an unprecedented rate, to help prevent contracting the virus. Some drugs have also been shown to have therapeutic effects in treating the covid-19 virus.

Most of the drugs that have been effective in treating the virus have been antivirals and immunomodulators, with r and monoclonal antibody cocktails being the only successful antiviral therapies, so far. This project aims to find other novel drug combinations with antiviral activity against SARS-CoV-2 and therefore covid-19.

The project is a collaboration of experts from three research institutions at Queen’s University Belfast, University of Liverpool and University of Oxford. The starting point will be screening 140 drugs that are known to have antiviral activity against SARS-CoV-2 to find combinations that enhance those drugs’ antiviral potential. Once the most effective combinations are identified, robust in vitro and in vivo trials will begin to validate each combination’s potential. The team will be able to then recommend potential combinations to progress to clinical trials.

An additional stage of the project entails screening two other large drug libraries that haven’t been screened yet, so that back-up drug combinations are identified. This will ensure a pipeline of antiviral drugs against SARS-CoV-2 for the future.

CELT's Objectives

  • Validate a drug screening pipeline platform for robust and rapid progression of combination drugs from identification to pre-clinical efficacy confirmation
  • Identify novel drug combinations with enhanced antiviral activities against SARS-CoV-2 compared to the respective single drugs from a custom 140 drug library
  • Investigate the propensity for development of drug resistant virus mutants
  • Exploit our drug screen platform for non-biased screening of a custom large-scale unexplored drug library (>4000 drugs) for novel combination antiviral treatments for COVID-19 to ensure a pipeline of promising therapeutics for the future
  • Determine the potential to exploit drug combination hits in clinical trial by pharmacometric modelling in silico
  • Determine the therapeutic potential of the top ranked (10 max) drug combination hits in our WD-PAEC/SARS-CoV-2 infection model
  • Determine the antiviral potential of the top ranked (10 max) drug combination hits in vivo in our rodent models of SARSCoV-2 infection.

Awarding body

Related publications

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