@article{fdi:010093044,
  title = {{G}enomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to {M}osnodenvir},
  author = {{B}ouzidi, {H}.{S}. and {S}en, {S}. and {P}iorkowski, {G}. and {P}ezzi, {L}. and {A}yhan, {N}. and {F}ontaine, {A}. and {C}anivez, {T}. and {G}eulen, {M}. and {A}maral, {R}. and {G}rard, {G}. and {D}urand, {G}.{A}. and {D}e {L}amballerie, {X}. and {T}ouret, {F}ranck and {K}litting, {R}.},
  editor = {},
  language = {{ENG}},
  abstract = {{D}engue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. {M}osnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. {H}ere, by analyzing dengue virus ({DENV}) genomes from the 2023-2024 epidemic in the {F}rench {C}aribbean {I}slands, we show that they all exhibit mutation {NS}4{B}:{V}91{A}, previously associated with a marked decrease in sensitivity to mosnodenvir in vitro. {U}sing antiviral activity tests on four clinical and reverse-genetic strains, we confirm a marked decrease in mosnodenvir sensitivity for {DENV}-2 (>1000 fold). {F}inally, combining phylogenetic analysis and experimental testing for resistance, we find that virus lineages with low sensitivity to mosnodenvir due to the {V}91{A} mutation likely emerged multiple times over the last 30 years in {DENV}-2 and {DENV}-3. {T}hese results call for increased genomic surveillance, in particular to track lineages with resistance mutations. {T}hese efforts should allow to better assess the activity profile of {DENV} treatments in development against circulating strains.},
  keywords = {{GUADELOUPE} ; {MARTINIQUE} ; {SAINT} {MARTIN} {ILE} ; {SAINT} {BARTHELEMY}},
  booktitle = {},
  journal = {{N}ature {C}ommunications},
  volume = {15},
  numero = {1},
  pages = {8667 [11 ]},
  ISSN = {2041-1723},
  year = {2024},
  DOI = {10.1038/s41467-024-52819-z},
  URL = {https://www.documentation.ird.fr/hor/fdi:010093044},
}