Beelontally, R. et al. (2017) Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins. Antiviral Research, 138, pp. 61-67. (doi: 10.1016/j.antiviral.2016.12.006) (PMID:27956134) (PMCID:PMC5244968)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Lau, Dr Betty and Wilkie, Dr Gavin and Davison, Professor Andrew |
| Authors: | Beelontally, R., Wilkie, G. S., Lau, B., Goodmaker, C. J., Ho, C. M.K., Swanson, C. M., Deng, X., Wang, J., Gray, N. S., Davison, A. J., and Strang, B. L. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Antiviral Research |
| Publisher: | Elsevier |
| ISSN: | 0166-3542 |
| ISSN (Online): | 1872-9096 |
| Published Online: | 09 December 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Antiviral Research 138:61-67 |
| Publisher Policy: | Reproduced under a creative commons license |
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