De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report.
Figure: Significance between WT and E802D mutants was assessed by unpaired, two-sample t tests, **p < 0.01 (p = 0.002 at 24 h, p = 0.006 at 48 h).
Figure: b Allele frequencies of E802D in nsp12 as ascertained by whole genome sequencing.
Figure: d Viral growth curves from icSARS-CoV-2 mNG WT, E802D (patient), and E802A (control) nsp12 mutants on a ORF7a depleted backbone.
Discussion: E802D is associated with a fitness cost in vitro, which may limit the broader impact of this mutation on the development of secondary resistance during treatment and the risk for primary resistance through transmission of resistant variants.
Discussion: In summary, we identified the de novo emergenc
In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2.
Abstract: Introduction of the NSP12 E802D mutation into our SARS-CoV-2 reverse genetics backbone confirmed its role in decreasing RDV sensitivity in vitro.
Result: While both stocks had high infectious titres (rSARS-CoV-2, ~2.5 x 107 pfu/ml and rNSP12-E802D, ~8.13 x 107 pfu/ml), there was a difference in the equivalent genome copies (GE)/ml, with rNSP12-E802D a ~0.5 log10 higher (rSARS-CoV-2, 7.16 x 108 GE/ml and rNSP12-E802D, 2.90 x 109 GE
Result: Whilst we thought it was unlikely to play a role, we also recovered virus with I168T mutation in NSP6 either alone or in combination with the NSP12 mutations (E802D or E802A).
SARS_CoV_2 mutation literature information.
PMID: 
2022
Nature communications
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