• TUCS Publication Series
• How to Publish in TUCS Series
• Publication Search
• Publication Graph
• Publication Input
• Publication Input Guide
• JuFo Browser

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 Brabande, Xavier Saelens, Denis E. Kainov, Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza a Virus Infection. Journal of Biological Chemistry 287, 35324–35332, 2012.

http://dx.doi.org/10.1074/jbc.M112.392142

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.

BibTeX entry:

@ARTICLE{jDeKaFeStNaLaYaAiKaAhKuVaKaTyJuKaPaHuElDeSaKa12a,
  title = {Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza a Virus Infection},
  author = {Denisova, Oxana V. and Kakkola, Laura and Feng, Lin and Stenman, Jakob and Nagaraj, Ashwini and Lampe, Johanna and Yadav, Bhagwan and Aittokallio, Tero and Kaukinen, Pasi and Ahola, Tero and Kuivanen, Suvi and Vapalahti, Olli and Kantele, Anu and Tynell, Janne and Julkunen, Ilkka and Kallio-Kokko, Hannimari and Paavilainen, Henrik and Hukkanen, Veijo and Elliott, Richard M. and De Brabande, Jef K. and Saelens, Xavier and Kainov, Denis E.},
  journal = {Journal of Biological Chemistry},
  volume = {287},
  pages = {35324–35332},
  year = {2012},
}

Belongs to TUCS Research Unit(s): Biomathematics Research Unit (BIOMATH)

Publication Forum rating of this publication: level 1

Edit publication