Combination of MEK inhibitors and oseltamivir leads to synergistic antiviral effects after influenza A virus infection in vitro

Haasbach, Emanuel; Hartmayer, Carmen; Planz, Oliver

doi:10.1016/j.antiviral.2013.03.006

Cited by 48 publications

(34 citation statements)

References 21 publications

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“…During replication, the influenza virus activates the Raf/MEK/ERK-cascade and the transcription factor NF-kB. This results in both virus supportive and antiviral effects by promoting viral genome transport for virus assembly and by inducing expression of proinflammatory host factors [50]. 1,8-Cineol treatment might interfere with this chain of events by inhibiting signaling via NF-kB during influenza infection, suppressing virus production and inflammatory responses.…”

Section: Discussionmentioning

confidence: 98%

1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice

Lai

Wang

et al. 2016

Inflammation

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1,8-Cineol is a major monoterpene principally from eucalyptus essential oils and has been shown to exert anti-inflammatory, antiviral, and inhibitory of nuclear factor (NF)-kB effect. In the present study, we evaluated the effect of 1,8-cineol on mice infected with influenza A virus. We found that 1,8-cineol protects against influenza viral infection in mice. Moreover, 1,8-cineol efficiently decreased the level of IL-4, IL-5, IL-10, and MCP-1 in nasal lavage fluids and the level of IL-1β, IL-6, TNF-α, and IFN-γ in lung tissues of mice infected with influenza virus. The results also showed that 1,8-cineol reduced the expression of NF-kB p65, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in lung tissues. Thus, 1,8-cineol appears to be able to augment protection against IFV infection in mice via attenuation of pulmonary inflammatory responses.

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Section: Discussionmentioning

confidence: 98%

1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice

Lai

Wang

et al. 2016

Inflammation

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“…Combination therapy, using drugs that target different components of the virus life cycle, has proven to offer advantages over drug monotherapy against several viral infections, including HIV (55), hepatitis C virus (56), and influenza A virus (57). Ribavirin, currently the only antiviral drug used against arenaviruses, and A3 target different metabolic pathways within the cell.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Arenavirus by A3, a Pyrimidine Biosynthesis Inhibitor

Ortiz-Riaño

Ngo

DeVito

et al. 2014

J Virol

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dArenaviruses merit significant interest as important human pathogens, since several of them cause severe hemorrhagic fever disease that is associated with high morbidity and significant mortality. Currently, there are no FDA-licensed arenavirus vaccines available, and current antiarenaviral therapy is limited to an off-labeled use of the nucleoside analog ribavirin, which has limited prophylactic efficacy. The pyrimidine biosynthesis inhibitor A3, which was identified in a high-throughput screen for compounds that blocked influenza virus replication, exhibits a broad-spectrum antiviral activity against negative-and positive-sense RNA viruses, retroviruses, and DNA viruses. In this study, we evaluated the antiviral activity of A3 against representative Old World (lymphocytic choriomeningitis virus) and New World (Junin virus) arenaviruses in rodent, monkey, and human cell lines. We show that A3 is significantly more efficient than ribavirin in controlling arenavirus multiplication and that the A3 inhibitory effect is in part due to its ability to interfere with viral RNA replication and transcription. We document an additive antiarenavirus effect of A3 and ribavirin, supporting the potential combination therapy of ribavirin and pyrimidine biosynthesis inhibitors for the treatment of arenavirus infections.

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“…Four other MEK inhibitors (Fig. C), PD‐0325901 , AZD‐6244 , AZD‐8330 , and RDEA‐119 (which are all orally available and at least in Phase 1 clinical trials for cancer therapy) demonstrated antiviral activity in vitro as single agents or in combination with oseltamivir . Also, the multiple kinase inhibitor WV970 (Fig.…”

Section: Strategies To Interfere With the Influenza Virus Polymerasementioning

confidence: 99%

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

Stevaert

Naesens

2016

Medicinal Research Reviews

138

151

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Influenza viruses cause seasonal epidemics and pandemic outbreaks associated with significant morbidity and mortality, and a huge cost. Since resistance to the existing anti‐influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given its critical role in virus replication and high degree of conservation among influenza A (of human or zoonotic origin) and B viruses. We here review the major progress that has been made in recent years in unravelling the structure and functions of this protein complex, enabling structure‐aided drug design toward the core regions of the PA endonuclease, PB1 polymerase, or cap‐binding PB2 subunit. Alternatively, inhibitors may target a protein–protein interaction site, a cellular factor involved in viral RNA synthesis, the viral RNA itself, or the nucleoprotein component of the viral ribonucleoprotein. The latest advances made for these diverse pharmacological targets have yielded agents in advanced (i.e., favipiravir and VX‐787) or early clinical testing, besides several experimental inhibitors in various stages of development, which are all covered here.

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Combination of MEK inhibitors and oseltamivir leads to synergistic antiviral effects after influenza A virus infection in vitro

Cited by 48 publications

References 21 publications

1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice

1, 8-Cineol Protect Against Influenza-Virus-Induced Pneumonia in Mice

Inhibition of Arenavirus by A3, a Pyrimidine Biosynthesis Inhibitor

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

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