دورية أكاديمية
Development of a cellular high-content, immunofluorescent HBV core assay to identify novel capsid assembly modulators that induce the formation of aberrant HBV core structures.
| العنوان: | Development of a cellular high-content, immunofluorescent HBV core assay to identify novel capsid assembly modulators that induce the formation of aberrant HBV core structures. |
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| المؤلفون: | Sauviller S; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Vergauwen K; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Jaensch S; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Gustin E; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Peeters D; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Vermeulen P; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Wuyts D; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Vandyck K; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Pauwels F; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium., Berke JM; Janssen Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: jberke@its.jnj.com. |
| المصدر: | Journal of virological methods [J Virol Methods] 2021 Jul; Vol. 293, pp. 114150. Date of Electronic Publication: 2021 Apr 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8005839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0984 (Electronic) Linking ISSN: 01660934 NLM ISO Abbreviation: J Virol Methods Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier/North-Holland Biomedical Press, 1980- |
| مواضيع طبية MeSH: | Capsid* , Hepatitis B virus*, Pyrimidines ; Virus Assembly ; Virus Replication |
| مستخلص: | Hepatitis B Virus (HBV) core protein has multiple functions in the viral life cycle and is an attractive target for new anti-viral therapies. Capsid assembly modulators (CAMs) target the core protein and induce the formation of either morphologically normal (CAM-N) or aberrant structures (CAM-A), both devoid of genomic material. To date a diverse family of CAM-N chemotypes has been identified, but in contrast, described CAM-As are based on the heteroaryldihydropyrimidine (HAP) scaffold. We used the HBV-inducible HepG2.117 cell line with immunofluorescent labeling of HBV core to develop and validate a cellular high-content image-based assay where aggregated core structures are identified using image analysis spot texture features. Treatment with HAPs led to a dose- and time-dependent formation of aggregated core appearing as dot-like structures in the cytoplasm and nucleus. By combining a biochemical and cellular screening approach, a compound was identified as a novel non-HAP scaffold able to induce dose-dependent formation of aberrant core structures, which was confirmed by electron microscopy and native gel electrophoresis. This compound displayed anti-HBV activity in HepG2.117 cells, providing proof-of-concept for our screening approach. We believe our combined biochemical and cellular high-content screening method will aid in expanding the range of CAM-A chemotypes. (Copyright © 2021 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Aberrant core structures; Capsid assembly modulator; HBV core; Hepatitis B; High-content; Non-HAP scaffold |
| المشرفين على المادة: | 0 (Pyrimidines) 0 (heteroaryldihydropyrimidine) |
| تواريخ الأحداث: | Date Created: 20210411 Date Completed: 20211124 Latest Revision: 20211124 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.jviromet.2021.114150 |
| PMID: | 33839187 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0984 |
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| DOI: | 10.1016/j.jviromet.2021.114150 |