Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection

Oxana V. Denisova, Laura Kakkola, Lin Feng, Jakob Stenman, Ashwini Nagaraj, Johanna Lampe, Bhagwan Yadav, Tero Aittokallio, Pasi Kaukinen, Tero Ahola, Suvi Kuivanen, Olli Vapalahti, Anu Kantele, Janne Tynell, Ilkka Julkunen, Hannimari Kallio-Kokko, Henrik Paavilainen, Veijo Hukkanen, Richard M. Elliott, Jef K. De BrabanderXavier Saelens, Denis E. Kainov

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)35324-35332
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number42
DOIs
StatePublished - Oct 12 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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., ... Kainov, D. E. (2012). Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection. Journal of Biological Chemistry, 287(42), 35324-35332. https://doi.org/10.1074/jbc.M112.392142