Host cell targeting of EGF receptors as novel broad spectrum drugs against Respiratory Syncytial Viruses and Corona viruses

Purpose: Respiratory syncytial virus (RSV) is a pandemic virus with profound infant mortality and morbidity.

Our screening of host target compounds for anti-RSV effect revealed that inhibitors of epidermal growth factor receptor (EGFR) exhibited potent antiviral activity, a finding we will exploit for antiviral drug development.Project organisation: Bergströms group has a track record of antiviral innovation (PI, GU); Arnberg (UmU), will be responsible for testing of drugs in Air-liquid-interface (ALI) human respiratory cell cultures, and Nyström (GU) will perform COVID-19 testing at the BSL-3 laboratory.

Through the Open Innovation platform of ASTRA-Zeneca, 1300 EGFR inhibitors are provided.

Support from the infrastructure in chemistry, CBCS (Chemical Biology Concortium, Sweden) is vital.Activity plan: Since EGFR inhibitors are in clinical use for lung cancer, compounds with anti-RSV activity and low toxicity as related to approved EGFR-targeting drugs were selected. Several other EGFR inhibitors from the OI platform also showed promising results as anti-RSV drugs.

Here, as a proof-of-concept, we will define anti-RSV and anti-COVID-19 activity of inhibitor 12 and other EGFR inhibitors in ALI cultures mimicking the human respiratory epithelium.

Since some of these compounds are already in clinical use, the pathway to  implementation can be short.Importance: a broad spectrum antiviral drug against RSV and other respiratory viruses will constitute a major medical break-through.