Recent Advances of Non-Nucleoside Polymerase Inhibitors With Broad-Spectrum Antiviral Activities

A tremendous and painful price has been paid in the fight against pandemic viruses in the global health field. Emerging and re-emerging viruses serve as primary drivers of severe pandemics, such as influenza virus (IV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Viral polymerases are highly conserved among viruses of the same genus. Inhibitors targeting polymerases often exhibit broad-spectrum antiviral activity against these same genus viruses, playing a crucial role in antiviral therapies. Non-nucleoside polymerase inhibitors demonstrate their superiority in terms of safety and anti-mutation ability out of nucleoside/nucleotide polymerase inhibitors. This review presents an overview of non-nucleoside polymerase inhibitors along with their relative antiviral activities and mechanisms of action, providing a reference for the development of novel antiviral drugs with broad-spectrum activities.