AB-343

AB-343 is a covalent small-molecule inhibitor of the SARS-CoV-2 main protease (Mpro, also known as 3CLpro), which is essential for viral replication. Developed by Arbutus Biopharma, the compound was designed to provide pan-coronavirus activity against both alpha and beta coronaviruses and maintain potency against variants resistant to first-generation inhibitors like nirmatrelvir. AB-343 demonstrated a favorable drug-drug interaction profile in preclinical studies, notably not requiring ritonavir boosting. Although IND-enabling studies were completed, Arbutus discontinued the development of AB-343 in late 2023 to prioritize its Hepatitis B virus (HBV) therapeutic programs.