title: RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms.
abstract: RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication within the infected cells. RdRP function is critical not only for the virus life cycle but also for its adaptive potential. The combination of low fidelity of replication and the absence of proofreading and excision activities within the RdRPs result in high mutation frequencies that allow these viruses a rapid adaptation to changing environments. In this review, we summarize the current knowledge about structural and functional aspects on RdRP catalytic complexes, focused mainly in the Picornaviridae family. The structural data currently available from these viruses provided high-resolution snapshots for a range of conformational states associated to RNA template-primer binding, rNTP recognition, catalysis and chain translocation. As these enzymes are major targets for the development of antiviral compounds, such structural information is essential for the design of new therapies.
authors.affiliation: Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park (PCB), Baldiri i Reixac 10, Barcelona E-08028, Spain. cfocri@ibmb.csic.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferrer-Orta
authors.affiliation: Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park (PCB), Baldiri i Reixac 10, Barcelona E-08028, Spain. dfecri@ibmb.csic.es.
authors.forename: Diego
authors.initials: D
authors.lastname: Ferrero
authors.affiliation: Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park (PCB), Baldiri i Reixac 10, Barcelona E-08028, Spain. nvmcri@ibmb.csic.es.
authors.forename: Núria
authors.initials: N
authors.lastname: Verdaguer
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D010849:Picornaviridae / Q000201:enzymology* / Q000502:physiology*; D011487:Protein Conformation; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D012324:RNA-Dependent RNA Polymerase
keywords: RNA-dependent RNA polymerase; picornaviruses; positive-strand RNA viruses; replication fidelity; viral replication