Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection

Denisova, O. V. et al. (2012) Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection. Journal of Biological Chemistry, 287(42), pp. 35324-35332. (doi: 10.1074/jbc.M112.392142)

Full text not currently available from Enlighten.

Abstract

Influenza A viruses (IAVs) infect humans and cause significant morbidity and mortality. Different treatment options have been developed; however, these were insufficient during recent IAV outbreaks. Here, we conducted a targeted chemical screen in human nonmalignant cells to validate known and search for novel host-directed antivirals. The screen validated saliphenylhalamide (SaliPhe) and identified two novel anti-IAV agents, obatoclax and gemcitabine. Further experiments demonstrated that Mcl-1 (target of obatoclax) provides a novel host target for IAV treatment. Moreover, we showed that obatoclax and SaliPhe inhibited IAV uptake and gemcitabine suppressed viral RNA transcription and replication. These compounds possess broad spectrum antiviral activity, although their antiviral efficacies were virus-, cell type-, and species-specific. Altogether, our results suggest that phase II obatoclax, investigational SaliPhe, and FDA/EMEA-approved gemcitabine represent potent antiviral agents.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Elliott, Professor Richard
Authors: Denisova, O. V., Kakkola, L., Feng, L., Stenman, J., Nagaraj, A., Lampe, J., Yadav, B., Aittokallio, T., Kaukinen, P., Ahola, T., Kuivanen, S., Vapalahti, O., Kantele, A., Tynell, J., Julkunen, I., Kallio-Kokko, H., Paavilainen, H., Hukkanen, V., Elliott, R.M., De Brabander, J. K., Saelens, X., and Kainov, D. E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Biological Chemistry
ISSN:0021-9258
ISSN (Online):1067-8816

University Staff: Request a correction | Enlighten Editors: Update this record