Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm

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Front Immunol. 2019 Jun 21;10:1393. doi: 10.3389/fimmu.2019.01393. eCollection 2019.
[h=1]Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm.[/h] Chen S[SUP]1,[/SUP][SUP]2[/SUP], Liu G[SUP]1,[/SUP][SUP]2[/SUP], Chen J[SUP]1[/SUP], Hu A[SUP]1,[/SUP][SUP]2[/SUP], Zhang L[SUP]1,[/SUP][SUP]2[/SUP], Sun W[SUP]1,[/SUP][SUP]2[/SUP], Tang W[SUP]1[/SUP], Liu C[SUP]1[/SUP], Zhang H[SUP]1[/SUP], Ke C[SUP]3[/SUP], Wu J[SUP]4[/SUP], Chen X[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Excessive inflammation associated with the uncontrolled release of pro-inflammatory cytokines is the main cause of death from influenza virus infection. Previous studies have indicated that inhibition of interferon gamma-induced protein 10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), or their cognate receptors has beneficial effects. Here, by using monocytic U937 cells that capable of secreting the three important cytokines during influenza A virus infection, we measured the inhibitory activities on the production of three cytokines of six anti-inflammatory compounds reported in other models of inflammation. We found that ponatinib had a highly inhibitory effect on the production of all three cytokines. We tested ponatinib in a mouse influenza model to assess its therapeutic effects with different doses and administration times and found that the delayed administration of ponatinib was protective against lethal influenza A virus infection without reducing virus titers. Therefore, we suggest that ponatinib may serve as a new immunomodulator in the treatment of influenza.


[h=4]KEYWORDS:[/h] cytokine storm; immunomodulator; influenza A virus; ponatinib; pro-inflammatory cytokine

PMID: 31293574 PMCID: PMC6598400 DOI: 10.3389/fimmu.2019.01393

 

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Front Immunol. 2019 Jun 21;10:1366. doi: 10.3389/fimmu.2019.01366. eCollection 2019.
[h=1]Peptide Antiviral Strategies as an Alternative to Treat Lower Respiratory Viral Infections.[/h] Nyanguile O[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Lower respiratory infection caused by human pathogens such as influenza and respiratory syncytial virus (RSV) is a significant healthcare burden that must be addressed. The preferred options to achieve this goal are usually to develop vaccines for prophylaxis and to develop antiviral small molecules to treat infected patients with convenient, orally administrable drugs. However, developing a vaccine against RSV poses special challenges with the diminished immune system of infants and the elderly, and finding a universal flu vaccine is difficult because the product must target a large array of viral strains. On the other hand, the use of small-molecule antivirals can result in the emergence of resistant viruses as it has well-been reported for HIV, influenza, and hepatitis C virus (HCV). This paper reviews peptide antiviral strategies as an alternative to address these challenges. The discovery of influenza and RSV peptidic fusion inhibitors will be discussed and compared to small molecules in view of escape mutations. The importance of constraining peptides into macrocycles to improve both their inhibitory activity and pharmacological properties will be highlighted.


[h=4]KEYWORDS:[/h] RSV; antivirals; escape mutation; fusion; influenza; peptides

PMID: 31293570 PMCID: PMC6598224 DOI: 10.3389/fimmu.2019.01366