Journal
NATURE REVIEWS MICROBIOLOGY
Volume 19, Issue 5, Pages 303-318Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41579-020-00501-8
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Funding
- Wellcome Trust [206579/Z/17/Z]
- Royal Society [206579/Z/17/Z]
- National Institutes of Health [R21AI147172]
- Wellcome Investigator Award [200835/Z/16/Z]
- UK Medical Research Council [MR/R009945/1]
- Wellcome Trust [206579/Z/17/Z, 200835/Z/16/Z] Funding Source: Wellcome Trust
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RNA viruses, including important human and animal pathogens, have genomes consisting of single or multiple RNA segments. Replication and transcription are performed by RNA-dependent RNA polymerases, and recent high-resolution studies have provided insights into the structures of these enzymes and their roles in viral transcription and replication, offering potential targets for antiviral drug design.
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 similar to 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.
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