Targeting structural dynamics of the RNA-dependent RNA polymerase for anti-viral strategies

David D. Boehr, Xinran Liu, Xiaorong Yang

Research output: Contribution to journalReview article

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalCurrent Opinion in Virology
Volume9
DOIs
StatePublished - Jan 1 2014

Fingerprint

RNA Replicase
Viruses
Attenuated Vaccines
Drug Design
RNA Viruses
Amino Acid Substitution
Molecular Dynamics Simulation
Catalytic Domain
Magnetic Resonance Spectroscopy
Genome
Proteins

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

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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.",
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Targeting structural dynamics of the RNA-dependent RNA polymerase for anti-viral strategies. / Boehr, David D.; Liu, Xinran; Yang, Xiaorong.

In: Current Opinion in Virology, Vol. 9, 01.01.2014, p. 194-200.

Research output: Contribution to journalReview article

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