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Basic Characteristics of Mutations
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Mutation Site
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T7001C |
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Mutation Site Sentence
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We found that the NS4B:V91A mutation (corresponding to a T to C transition at position 7001 in the CDS) was present in all DENV sequenced from the epidemic (Supplementary Table 1). |
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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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NS4B |
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Standardized Encoding Gene
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NS4B
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Genotype/Subtype
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DENV-2 Genotype II;DENV-2 Genotype III;DENV-2 Genotype V;DENV-3 Genotype II;DENV-3 Genotype III |
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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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Cell line
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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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- |
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Treatment
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mosnodenvir |
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Location
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- |
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Literature Information
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PMID
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39384752
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Title
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Genomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to Mosnodenvir
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Author
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Bouzidi HS,Sen S,Piorkowski G,Pezzi L,Ayhan N,Fontaine A,Canivez T,Geulen M,Amaral R,Grard G,Durand GA,de Lamballerie X,Touret F,Klitting R
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Journal
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Nature communications
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Journal Info
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2024 Oct 9;15(1):8667
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Abstract
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Dengue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. Here, by analyzing dengue virus (DENV) genomes from the 2023-2024 epidemic in the French Caribbean Islands, we show that they all exhibit mutation NS4B:V91A, previously associated with a marked decrease in sensitivity to mosnodenvir in vitro. Using antiviral activity tests on four clinical and reverse-genetic strains, we confirm a marked decrease in mosnodenvir sensitivity for DENV-2 ( > 1000 fold). Finally, combining phylogenetic analysis and experimental testing for resistance, we find that virus lineages with low sensitivity to mosnodenvir due to the V91A mutation likely emerged multiple times over the last 30 years in DENV-2 and DENV-3. These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains.
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Sequence Data
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-
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