The Journal of biological chemistry · 2012
Obatoclax, saliphenylhalamide, and gemcitabine inhibit influenza a virus infection.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Denisova Oxana V, Kakkola Laura, Feng Lin, Stenman Jakob, Nagaraj Ashwini, Lampe Johanna, Yadav Bhagwan, Aittokallio Tero, Kaukinen Pasi, Ahola Tero, Kuivanen Suvi, Vapalahti Olli, Kantele Anu, Tynell Janne, Julkunen Ilkka, Kallio-Kokko Hannimari, Paavilainen Henrik, Hukkanen Veijo, Elliott Richard M, De Brabander Jef K, Saelens Xavier, Kainov Denis E
Аннотация
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.