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Basic Characteristics of Mutations
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Mutation Site
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L227F |
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Mutation Site Sentence
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Table 2 |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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M |
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Standardized Encoding Gene
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M
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Genotype/Subtype
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Delta(AY.116) |
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Viral Reference
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-
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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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NTV/r RAMs |
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Location
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Botswana |
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Literature Information
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PMID
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39015352
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Title
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Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana
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Author
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Choga WT,Bareng OT,Moraka NO,Maruapula D,Gobe I,Ndlovu NS,Zuze BJL,Motshosi PC,Seru KB,Matsuru T,Boitswarelo M,Matshaba M,Gaolathe T,Mosepele M,Makhema J,Tamura TJM,Li JZ,Shapiro R,Lockman S,Gaseitsiwe S,Moyo S
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Journal
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Open forum infectious diseases
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Journal Info
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2024 Jul 2;11(7):ofae344
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Abstract
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BACKGROUND: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19). METHODS: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023. RESULTS: The sequenced 5254 samples included Beta variants of concerns (VOCs; n = 323), Delta VOCs (n = 1314), and Omicron VOCs (n = 3354). Overall, 77.8% of the sequences exhibited at least 1 polymorphism within 76/306 amino acid positions in the nsp5 gene. NTV/rRAMs were identified in 34/5254 (0.65%; 95% CI, 0.43%-0.87%) and occurred at 5 distinct positions. Among the NTV/r RAMS detected, A191V was the most prevalent (24/34; 70.6%). Notably, T21I mutation had a prevalence of 20.6% (7/34) and coexisted with either K90R (n = 3) polymorphism in Beta sequences with RAMs or P132H (n = 3) polymorphism for Omicron sequences with RAMs. Other NTV/r RAMs detected included P108S, with a prevalence of 5.88% (2/34), and L50F, with a prevalence of 2.94% (1/34). NTV/r RAMs were significantly higher (P < .001) in Delta (24/35) compared with Beta (4/34) and Omicron (6/34) sequences. CONCLUSIONS: The frequency of NTV/r RAMs in Botswana was low. Higher rates were observed in Delta VOCs compared to Omicron and Beta VOCs. As NTV/r use expands globally, continuous surveillance for drug-resistant variants is essential, given the RAMs identified in our study.
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Sequence Data
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-
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