Structural insights into RNA polymerases of negative-sense RNA viruses

• Published in: Nature reviews. Microbiology 2021-05, Vol.19 (5), p.303-318
• Main Authors: te Velthuis, Aartjan J. W., Grimes, Jonathan M., Fodor, Ervin
• Format: Article
• Language: English
• Subjects: 631/326/596/2148; 631/535; Animals; Antiviral agents; Biomedical and Life Sciences; DNA-Directed RNA Polymerases - chemistry; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; Drug development; Genetic aspects; Genomes; Humans; Infectious Diseases; Influenza; Life Sciences; Lyssavirus; Measles; Medical Microbiology; Microbiology; Molecular modelling; Parasitology; Physiological aspects; Protein Conformation; Rabies; Replication; Respiratory syncytial virus; Review; Review Article; RNA polymerases; RNA viruses; RNA Viruses - enzymology; Structure; Target recognition; Transcription; Viral diseases; Viral proteins; Viral Proteins - chemistry; Viral Proteins - genetics; Viral Proteins - metabolism; Virology; Viruses
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-020-00501-8

RNA viruses include many important human and animal pathogens, such as the influenza viruses, respiratory syncytial virus, Ebola virus, measles virus and rabies virus. The genomes of these viruses consist of single or multiple RNA segments that assemble with oligomeric viral nucleoprotein into ribonucleoprotein complexes. Replication and transcription of the viral genome is performed by ~250–450 kDa viral RNA-dependent RNA polymerases that also contain capping or cap-snatching activity. In this Review, we compare recent high-resolution X-ray and cryoelectron microscopy structures of RNA polymerases of negative-sense RNA viruses with segmented and non-segmented genomes, including orthomyxoviruses, peribunyaviruses, phenuiviruses, arenaviruses, rhabdoviruses, pneumoviruses and paramyxoviruses. In addition, we discuss how structural insights into these enzymes contribute to our understanding of the molecular mechanisms of viral transcription and replication, and how we can use these insights to identify targets for antiviral drug design. In this Review, Fodor and colleagues discuss recent structural insights into the RNA polymerases of negative-sense RNA viruses and their use to identify novel targets for the development of antiviral agents.