Polymerases of paramyxoviruses and pneumoviruses

The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.