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Infectious disease

SARS-associated coronavirus

Exoribonuclease in nonstructural protein 14

In vitro studies suggest nsp14-ExoN inhibitors could help sensitize coronaviruses to RNA mutagen therapeutics including ribavirin. In murine hepatitis virus coronaviruses, knockout of the RNA proofreading gene nsp14-ExoN increased sensitivity to 5-fluorouracil and ribavirin by 300-fold and decreased viral replication compared with no knockout. In nsp14-ExoN-deficient SARS viruses, 5-fluorauracil treatment induced 16-fold more mutations than those seen in wild-type viruses. Next steps could include identifying and evaluating pharmacological nsp14-ExoN inhibitors in animal infection models.

SciBX 6(36); doi:10.1038/scibx.2013.998
Published online Sept. 19, 2013

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Smith, E.C. et al. PLoS Pathog.; published online Aug. 15, 2013;
Contact: Mark R. Denison, Vanderbilt University Medical Center,
Nashville, Tenn.