Murine models of dengue virus infection for novel drug discovery
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/β 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Expert opinion on drug discovery - 17(2022), 4 vom: 03. Apr., Seite 397-412 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Byrne, Alana B [VerfasserIn] |
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| Links: |
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| Themen: |
AG129 mice |
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| Anmerkungen: |
Date Completed 05.04.2022 Date Revised 30.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17460441.2022.2033205 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM336325991 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a EXPERT OPINION: At present, there is no murine model that fully recapitulates human disease. However, immunocompromised mice deficient in IFN-α/β 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Damonte, Elsa B |e verfasserin |4 aut | |
| 700 | 1 | |a Talarico, Laura B |e verfasserin |4 aut | |
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