Research Progress on the Structural Biology of Paramyxovirus Polymerase and Its Inhibitors

The family Paramyxoviridae comprises nonsegmented, negative-sense RNA viruses (nsNSV), including key pathogens like Nipah, measles, and parainfluenza viruses. The lack of approved specific therapeutics against paramyxoviruses, alongside concerns such as vaccine hesitancy and reduced efficacy for certain existing vaccines, presents a major challenge to global public health. There is an urgent need to develop broad-spectrum antiviral drugs, and the paramyxovirus polymerase complex has emerged as an ideal target owing to its conservation, specificity, and essential role in the viral life cycle. This Perspective synthesizes recent structural biology studies of various paramyxovirus polymerase complexes, discusses their commonalities and distinct features, and analyzes the mechanisms of existing inhibitors. We identify potential druggable sites and propose rational drug design strategies. It is expected that this work will serve as a valuable reference for advancing the development of related therapeutic interventions.