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Murine models of dengue virus infection for novel drug discovery.
Byrne, Alana B; García, Cybele C; Damonte, Elsa B; Talarico, Laura B.
Afiliação
  • Byrne AB; Laboratorio de Investigaciones Infectológicas y Biología Molecular, Infectología, Departamento de Medicina, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina.
  • García CC; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
  • Damonte EB; Laboratorio de Estrategias Antivirales, Departamento de Química Biológica-IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Talarico LB; Laboratorio de Estrategias Antivirales, Departamento de Química Biológica-IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Expert Opin Drug Discov ; 17(4): 397-412, 2022 Apr.
Article em En | MEDLINE | ID: mdl-35098849
INTRODUCTION: Dengue virus (DENV) is the causative agent of the most prevalent human disease transmitted by mosquitoes in tropical and subtropical regions worldwide. At present, no antiviral drug is available and the difficulties to develop highly protective vaccines against the four DENV serotypes maintain the requirement of effective options for dengue chemotherapy. AREAS COVERED: The availability of animal models that reproduce human disease is a very valuable tool for the preclinical evaluation of potential antivirals. Here, the main murine models of dengue infection are described, including immunocompetent wild-type mice, immunocompromised mice deficient in diverse components of the interferon (IFN) pathway and humanized mice. The main findings in antiviral testing of DENV inhibitory compounds in murine models are also presented. EXPERT OPINION: At present, there is no murine model that fully recapitulates human disease. However, immunocompromised mice deficient in IFN-α/ß and -γ receptors, with their limitations, have shown to be the most suitable system for antiviral preclinical testing. In fact, the AG129 mouse model allowed the identification of celgosivir, an inhibitor of cellular glucosidases, as a promising option for DENV therapy. However, clinical trials still were not successful, emphasizing the difficulties in the transition from preclinical testing to human treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Expert Opin Drug Discov Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Expert Opin Drug Discov Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido