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J Med Chem ; 67(5): 4063-4082, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482827

RESUMO

Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no dengue-specific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of JNJ-1802 as a potent, pan-serotype DENV inhibitor (EC50's ranging from 0.057 to 11 nM against the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a dose-proportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802 is being progressed in clinical studies for the prevention or treatment of dengue.


Assuntos
Vírus da Dengue , Dengue , Hidrocarbonetos Halogenados , Indóis , Camundongos , Humanos , Animais , Sorogrupo , Dengue/tratamento farmacológico
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