Structural Dynamics of Picornaviral RdRP Complexes. Implications for the Design of Antivirals

  • Núria Verdaguer
  • Cristina Ferrer-Orta
  • Esteban Domingo
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

Abstract

Genome replication in picornavirus is catalyzed by a virally encoded RNA dependent RNA polymerase, termed 3D. These viruses also use a small protein primer, named VPg to initiate RNA replication. Polymerase 3D also catalyzes the covalent linkage of UMP to a N-terminal tyrosine on VPg. Seven different crystal structures of foot-and-mouth disease virus (FMDV) 3D catalytic complexes have enhanced our understanding of template and primer recognition, VPg uridylylation and rNTP binding and catalysis. In addition, the biochemical and structural analyses of six different FMDV 3D ribavirin resistant mutants provided evidences of three different mechanisms of resistance to this mutagenic nucleoside analogue. Such structural information is providing new insights into the fidelity of RNA replication, and for the design of antiviral compounds.

Keywords

Picornavirus RNA-dependent RNA polymerase Replication fidelity Ribavirin 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Núria Verdaguer
    • 1
  • Cristina Ferrer-Orta
    • 1
  • Esteban Domingo
    • 2
  1. 1.Instituto de Biología Molecular de Barcelona CSIC, Parc Científic de BarcelonaBarcelonaSpain
  2. 2.Centro de Biología Molecular Severo Ochoa (CSIC-UAM), CantoblancoMadridSpain

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