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Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection

(2012) JOURNAL OF BIOLOGICAL CHEMISTRY. 287(42). p.35324-35332
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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.
Keywords
APOPTOSIS, CELLS, NUCLEOSIDE, EXPRESSION, PROTEINS, MCL-1, AGENTS

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Citation

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Chicago
Denisova, Oxana V, Laura Kakkola, Lin Feng, Jakob Stenman, Ashwin Nagaraj, Johanna Lampe, Bhagwan Yadav, et al. 2012. “Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection.” Journal of Biological Chemistry 287 (42): 35324–35332.
APA
Denisova, O. V., Kakkola, L., Feng, L., Stenman, J., Nagaraj, A., Lampe, J., Yadav, B., et al. (2012). Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(42), 35324–35332.
Vancouver
1.
Denisova OV, Kakkola L, Feng L, Stenman J, Nagaraj A, Lampe J, et al. Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection. JOURNAL OF BIOLOGICAL CHEMISTRY. 2012;287(42):35324–32.
MLA
Denisova, Oxana V, Laura Kakkola, Lin Feng, et al. “Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection.” JOURNAL OF BIOLOGICAL CHEMISTRY 287.42 (2012): 35324–35332. Print.
@article{3060853,
  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.},
  author       = {Denisova, Oxana V and Kakkola, Laura and Feng, Lin and Stenman, Jakob and Nagaraj, Ashwin 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 Brabander, Jef K and Saelens, Xavier and Kainov, Denis E},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {APOPTOSIS,CELLS,NUCLEOSIDE,EXPRESSION,PROTEINS,MCL-1,AGENTS},
  language     = {eng},
  number       = {42},
  pages        = {35324--35332},
  title        = {Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza A virus infection},
  url          = {http://dx.doi.org/10.1074/jbc.M112.392142},
  volume       = {287},
  year         = {2012},
}

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