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Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins.
- Source :
-
Antiviral research [Antiviral Res] 2017 Feb; Vol. 138, pp. 61-67. Date of Electronic Publication: 2016 Dec 09. - Publication Year :
- 2017
-
Abstract
- Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production.<br /> (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Antiviral Agents chemistry
Cell Line
Cytomegalovirus physiology
DNA Replication drug effects
High-Throughput Screening Assays
Humans
Transcription, Genetic drug effects
Viral Proteins biosynthesis
Viral Proteins genetics
Antiviral Agents pharmacology
Cytomegalovirus drug effects
Drug Discovery
Immediate-Early Proteins biosynthesis
Trans-Activators biosynthesis
Virus Replication drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 138
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 27956134
- Full Text :
- https://doi.org/10.1016/j.antiviral.2016.12.006