Article
Loss of nsp14-exonuclease activity impairs the replication, proofreading, fitness, and pathogenesis of SARS-CoV-2.
mBio - 10 Jun 2026
Anderson-Daniels Jordan, Diefenbacher Meghan V, Yount Boyd L, Meganck Rita M, Tse Longping V, Burke Kaitlyn N, Miranda Hector A, Scobey D Trevor, Lu Xiaotao, Stevens Laura, Dinnon Kenneth H, Chapman Nathaniel S, Pajon Camryn, Powers John M, Nguyen Cameron, Graham Rachel L, Heaton Nicholas S, Baric Ralph S, Denison Mark R, Sheahan Timothy P
Abstract excerpt
Coronaviruses (CoVs) replicate their RNA genomes with a higher degree of fidelity than other RNA viruses, a mechanism mediated by the proofreading and recombination activities of the exoribonuclease domain of replicase nonstructural protein 14 (nsp14-ExoN). Both murine hepatitis virus (MHV) and SARS-CoV tolerate nsp14-ExoN loss-of-function mutations (ExoN-) (D90A and E92A), but have impaired replication fidelity...
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