tetano
Editor, Senior Moderator
J Biol Chem. 2012 Aug 21. [Epub ahead of print]
Obatoclax, saliphenylhalamide and gemcitabine inhibit influenza A virus infection.
Denisova OV, 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 RM, De Brabander JK, Saelens X, Kainov DE.
Source
Institute for Molecular Medicine Finland, Finland;
Abstract
Influenza A viruses (IAV) 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 non-malignant 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, FDA/EMEA-approved gemcitabine represent potent antiviral agents.
PMID:
22910914
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22910914
Obatoclax, saliphenylhalamide and gemcitabine inhibit influenza A virus infection.
Denisova OV, 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 RM, De Brabander JK, Saelens X, Kainov DE.
Source
Institute for Molecular Medicine Finland, Finland;
Abstract
Influenza A viruses (IAV) 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 non-malignant 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, FDA/EMEA-approved gemcitabine represent potent antiviral agents.
PMID:
22910914
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22910914