Kinase inhibitors as broad spectrum antivirals against pandemic viruses

Purpose: Antiviral treatment against pandemic Respiratory syncytial virus (RSV), Measles virus (MV) and Polio Virus (PoV) are completely lacking.

The project aims to develop such drugs.Project organisation: This is a collaboration between Gothenburg University (GU), Linköping University (LiU) and Astra-Zeneca (AZ), connecting antiviral research, advanced cell culture models and drug development.Activity Plan: Our discovery of antiviral effects of inhibitors of Epidermal Growth Factor Receptor (EGFR) against RSV and of Mitogen Activated Protein 4 Kinase (MAP4K) against  PoV, has opened up a novel research field to be exploited for improved pandemic preparedness against these viruses.

Due to similarity between RSV and MV, we currently screen EGFR inhibitors also against this virus.As our two main proofs of concept (PoC) we will:i/ elucidate the mechanisms behind the high antiviral potency and low cellular toxicity of our lead compounds, i.e. to further define antiviral/cellular targetsii/ confirm the antiviral effect of these lead compounds in human respiratory and neuronal cells, differentiated from stem cells, instead of animal modelsInnovation potential and importance: the discoveries were made using a molecular library from AZ in which many compounds were proprietary, i.e. not publicly available.

The high antiviral activity and unique mechanisms of our lead compounds argues for potential drug development, which can counteract outbreaks of these pandemic viruses.