A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection




Julkaisun tekijät: 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
Kustantaja: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Julkaisuvuosi: 2012
Journal: Journal of Biological Chemistry
Tietokannassa oleva lehden nimi: JOURNAL OF BIOLOGICAL CHEMISTRY
Lehden akronyymi: J BIOL CHEM
Numero sarjassa: 42
Volyymi: 287
Julkaisunumero: 42
ISSN: 0021-9258

Tiivistelmä


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.



Last updated on 2019-29-01 at 16:55