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Basic Characteristics of Mutations
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Mutation Site
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G823G |
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Mutation Site Sentence
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Table 3 |
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Mutation Level
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Amino acid level |
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Mutation Type
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Synonymous substitution |
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Gene/Protein/Region
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NSP12 |
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Standardized Encoding Gene
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ORF1b
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Genotype/Subtype
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- |
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Viral Reference
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NC_045512.2
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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RDV |
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Location
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USA |
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Literature Information
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PMID
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37466213
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Title
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Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)
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Author
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Hedskog C,Rodriguez L,Roychoudhury P,Huang ML,Jerome KR,Hao L,Ireton RC,Li J,Perry JK,Han D,Camus G,Greninger AL,Gale M Jr,Porter DP
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Journal
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The Journal of infectious diseases
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Journal Info
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2023 Nov 2;228(9):1263-1273
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Abstract
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BACKGROUND: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19. METHODS: Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene. RESULTS: Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold). CONCLUSIONS: The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.
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Sequence Data
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-
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