title: Targeting structural dynamics of the RNA-dependent RNA polymerase for anti-viral strategies.
abstract: The RNA-dependent RNA polymerase is responsible for genome replication of RNA viruses. Nuclear magnetic resonance experiments and molecular dynamics simulations have indicated that efficient and faithful polymerase function requires highly coordinated internal protein motions. Interference with these motions, either through amino acid substitutions or small molecule binding, can disrupt polymerase and virus function. In particular, these studies have pointed toward highly conserved structural elements, like the motif-D active-site loop, that can be modified to generate polymerases with desired properties. Viruses encoding engineered polymerases might serve as live, attenuated vaccine strains. Further elucidation of polymerase structural dynamics will also provide new avenues for anti-viral drug design.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: ddb12@psu.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Boehr
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Xinran
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D012328:RNA Viruses / Q000187:drug effects* / Q000201:enzymology*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012324:RNA-Dependent RNA Polymerase