tetano
Editor, Senior Moderator
Antiviral Res. 2014 Sep 19. pii: S0166-3542(14)00271-X. doi: 10.1016/j.antiviral.2014.09.008. [Epub ahead of print]
In vitro anti-influenza A activity of interferon (IFN)-λ1 combined with IFN-β or oseltamivir carboxylate.
Ilyushina NA1, Donnelly RP2.
Author information
Abstract
Influenza viruses, which can cross species barriers and adapt to new hosts, pose a constant potential threat to human health. The influenza pandemic of 2009 highlighted the rapidity with which an influenza virus can spread worldwide. Currently available antivirals have a number of limitations against influenza, and novel antiviral strategies, including novel drugs and drug combinations, are urgently needed. Here, we evaluated the in vitro effects of interferon (IFN)-β, IFN-λ1, oseltamivir carboxylate (a neuraminidase (NA) inhibitor), and combinations of these agents against two seasonal (i.e., H1N1 and H3N2) influenza A viruses. We observed that A/California/04/09 (H1N1) and A/Panama/2007/99 (H3N2) isolates were similarly sensitive to the antiviral activity of IFN-β and oseltamivir carboxylate in A549 and Calu-3 cells. In contrast, IFN-λ1 exhibited substantially lower protective potential against the H1N1 strain (64-1030 fold ↓, P < 0.05), and was ineffective against H3N2 virus in both cell lines. Three dimensional analysis of drug-drug interactions revealed that IFN-λ1 interacted with IFN-β and oseltamivir carboxylate in an additive or synergistic manner, respectively, to inhibit influenza A virus replication in human airway epithelial cells. Overall, the present study demonstrated that anti-influenza agents with different mechanisms of action (e.g., a NA inhibitor combined with IFN-λ1) exerted a significantly greater (P < 0.05) synergistic effect compared to co-treatment with drugs that target the same signaling pathway (i.e., IFN-β plus IFN-λ1) in vitro. Our findings provide support for the combined use of interferon plus oseltamivir as a potential means for treating influenza infections.
Copyright ? 2014. Published by Elsevier B.V.
KEYWORDS:
Combination therapy; IFN-β; IFN-λ1; Influenza A virus; Oseltamivir carboxylate
PMID:
25245230
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25245230
In vitro anti-influenza A activity of interferon (IFN)-λ1 combined with IFN-β or oseltamivir carboxylate.
Ilyushina NA1, Donnelly RP2.
Author information
Abstract
Influenza viruses, which can cross species barriers and adapt to new hosts, pose a constant potential threat to human health. The influenza pandemic of 2009 highlighted the rapidity with which an influenza virus can spread worldwide. Currently available antivirals have a number of limitations against influenza, and novel antiviral strategies, including novel drugs and drug combinations, are urgently needed. Here, we evaluated the in vitro effects of interferon (IFN)-β, IFN-λ1, oseltamivir carboxylate (a neuraminidase (NA) inhibitor), and combinations of these agents against two seasonal (i.e., H1N1 and H3N2) influenza A viruses. We observed that A/California/04/09 (H1N1) and A/Panama/2007/99 (H3N2) isolates were similarly sensitive to the antiviral activity of IFN-β and oseltamivir carboxylate in A549 and Calu-3 cells. In contrast, IFN-λ1 exhibited substantially lower protective potential against the H1N1 strain (64-1030 fold ↓, P < 0.05), and was ineffective against H3N2 virus in both cell lines. Three dimensional analysis of drug-drug interactions revealed that IFN-λ1 interacted with IFN-β and oseltamivir carboxylate in an additive or synergistic manner, respectively, to inhibit influenza A virus replication in human airway epithelial cells. Overall, the present study demonstrated that anti-influenza agents with different mechanisms of action (e.g., a NA inhibitor combined with IFN-λ1) exerted a significantly greater (P < 0.05) synergistic effect compared to co-treatment with drugs that target the same signaling pathway (i.e., IFN-β plus IFN-λ1) in vitro. Our findings provide support for the combined use of interferon plus oseltamivir as a potential means for treating influenza infections.
Copyright ? 2014. Published by Elsevier B.V.
KEYWORDS:
Combination therapy; IFN-β; IFN-λ1; Influenza A virus; Oseltamivir carboxylate
PMID:
25245230
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25245230