Optimisation of a novel series of SARS-CoV-2 inhibitors

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The COVID-19 pandemic is the most serious global health crisis in recent history with over 140,000 deaths in the UK and over 5 million deaths worldwide. Despite extensive vaccination programs, the virus remains transmissible with hospitalisation and mortality remaining high, both in the UK and globally.Infex Therapeutics, in partnership with the University of Liverpool and the Liverpool School of Tropical Medicine, and supported by the Medicines Discovery Catapult, is developing a novel series of drugs to treat coronavirus, including SARS-CoV-2, the cause of the global COVID-19 pandemic. These new drugs work by targeting a key protease essential for viral replication. These inhibitors will help meet a desperate clinical need for novel anti-viral agents which are effective in treating breakthrough cases, unvaccinated and high-risk patients such as those undergoing anti-cancer treatments, leading to reduced hospitalisation and pressure on healthcare systems, and lower death rates. The compounds have potential to treat future SARS-CoV-2 variants and may have utility for use in predicted future pandemics due to the highly conserved nature of the target across different coronaviruses.The objective for this grant is to develop existing hits through lead optimisation to generate advanced drug-like leads, which display in vivo proof of concept in efficacy models and have high potential for preclinical candidate nomination and onwards development towards a safe and effective treatment. This will be achieved by applying a clearly-identified lead-optimisation program including medicinal chemistry, enzymology, virology, safety profiling and efficacy assessment. An innovative airway organoid model using human lung cells will be developed and utilised to aid the translation of preclinical data into clinical trials and will provide broader utility across the industry.