Skip to content

Research at St Andrews

Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice

Research output: Contribution to journalArticle


Andri Vasou, Christina Paulus, Janina Narloch, Zoe O. Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E. Randall, Catherine S. Adamson

School/Research organisations


Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets. To exploit this, we have successfully developed and executed a novel modular cell-based platform that facilitates the safe and rapid screening for inhibitors of a viral IFN antagonist of choice. The platform is based on two reporter cell-lines that provide a simple method to detect activation of IFN induction or signaling via an eGFP gene placed under the control of the IFNβ or an ISRE-containing promoter, respectively. Expression of a target IFN antagonist in the appropriate reporter cell-line will block the IFN response and hence eGFP expression. We hypothesized that addition of a compound that inhibits IFN antagonist function will release the block imposed on the IFN response and hence restore eGFP expression, providing a measurable parameter for high throughput screening (HTS). We demonstrate assay proof-of-concept by (i) exploiting hepatitis C virus (HCV) protease inhibitors to inhibit NS3-4A's capacity to block IFN induction and (ii) successfully executing two HTS targeting viral IFN antagonists that block IFN signaling; NS2 and IE1 from human respiratory syncytial virus (RSV) and cytomegalovirus (CMV) respectively, two clinically important viruses for which vaccine development has thus far been unsuccessful and new antivirals are required. Both screens performed robustly and Z′ Factor scores of >0.6 were achieved. We identified (i) four hit compounds that specifically inhibit RSV NS2's ability to block IFN signaling by mediating STAT2 degradation and exhibit modest antiviral activity and (ii) two hit compounds that interfere with IE1 transcription and significantly impair CMV replication. Overall, we demonstrate assay proof-of-concept as we target viral IFN antagonists from unrelated viruses and demonstrate its suitability for HTS.


Original languageEnglish
Pages (from-to)79-92
JournalAntiviral Research
Early online date14 Oct 2017
Publication statusPublished - Feb 2018

    Research areas

  • Viral interferon (IFN) antagonists, Antivirals, Human Respiratory Syncytial Virus (RSV), Human Cytomegalovirus (CMV), High-throughput screening (HTS), Signal transducer and activator of transcription 2 (STAT2)

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage

    Dunphy, G., Flannery, S. M., Almine, J. F., Connolly, D. J., Paulus, C., Jonsson, K. L., Jakobsen, M. R., Nevels, M. M., Bowie, A. G. & Unterholzner, L., 6 Sep 2018, In : Molecular Cell. 71, 5, p. 745-760 22 p., e5.

    Research output: Contribution to journalArticle

  2. Human cytomegalovirus immediate early 1 protein causes loss of SOX2 from neural progenitor cells by trapping unphosphorylated STAT3 in the nucleus

    Wu, C-C., Jiang, X., Wang, X-Z., Liu, X-J., Li, X-J., Yang, B., Ye, H-Q., Harwardt, T., Jiang, M., Xia, H-M., Wang, W., Britt, W. J., Paulus, C., Nevels, M. M. & Luo, M-H., Sep 2018, In : Journal of Virology. 92, 17, e00340-18.

    Research output: Contribution to journalArticle

  3. Impact of human cytomegalovirus on glioblastoma cell viability and chemotherapy treatment

    dos Santos, C. J., Ferreira Castro, F. L., de Aguiar, R. B., Menezes, I. G., Santos, A. C., Paulus, C., Nevels, M. & Carlan da Silva, M. C., Sep 2018, In : Journal of General Virology. 99, 9, p. 1274-1285 12 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Novel approaches to inhibiting HIV-1 replication

    Adamson, C. S. & Freed, E. O., 2010, In : Antiviral Research. 85, 1, p. 119-141

    Research output: Contribution to journalArticle

  2. Characteristics of arbidol-resistant mutants of influenza virus: Implications for the mechanism of anti-influenza action of arbidol

    Leneva, IA., Russell, R. J. M., Boriskin, YS. & Hay, AJ., Feb 2009, In : Antiviral Research. 81, p. 132-140 9 p.

    Research output: Contribution to journalArticle

ID: 251360897