Discovery of A-967079 as an Enterovirus D68 Antiviral by Targeting the Viral 2C Protein

Enterovirus D68 (EV-D68) has had several outbreaks worldwide, yet no FDA-approved Antiviral is available for treating this viral Infection. EV-D68 Infection typically leads to respiratory illnesses and, in severe cases, can cause neurological complications and even death, particularly in children. This study identified a small molecule, A-967079, as an EV-D68 Antiviral through phenotypical screening. A-967079 has shown potent and broad-spectrum Antiviral activity with a high selectivity index against multiple strains of EV-D68. Pharmacological characterization of the mechanism of action involving time-of-addition, Resistance Selection, and differential scanning fluorimetry assays suggests that viral 2C protein is the drug target. Overall, A-967079 represents a promising candidate for further development as an EV-D68 Antiviral.