Journal
ANTIVIRAL RESEARCH
Volume 143, Issue -, Pages 74-84Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2017.04.007
Keywords
Polyketide; Influenza A virus; EGFR pathway; Virus replication; Inflammatory responses
Categories
Funding
- National Natural Science Foundation of China [81302811, 81561148012, 81373298, 31500646]
- NSFC-Shandong [U1406402]
- NSFC-Guangdong [U1501221]
- Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province [BS2015YY040]
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Development of anti-influenza A virus (IAV) drugs with novel targets and low toxicity is critical for preparedness against influenza outbreaks. In the current study, our results indicated that the novel polyketide compound purpurquinone B (PPQ-B) derived from acid-tolerant fungus Penicillium purpurogenum strain JS03-21 suppressed the replication of IAV in vitro with low toxicity, and may block some stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34; PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009) virus replication in vitro, suggesting that PPQ-B possesses broad-spectrum anti-IAV activities. PPQ-B's antiviral activity may be largely related to its inhibition of some steps that occur 0-4 h after adsorption. Oral administration of PPQ-B could decrease pulmonary viral titers and improve survival rate in IAV infected mice. PPQ-B also significantly decreased the production of inflammatory factors TNF-alpha, IL-6, RANTES and KC in IAV infected lungs and A549 cells, suggesting that PPQ-B may also attenuate the inflammatory responses caused by IAV infection. PPQ-B may down-regulate the NF-kappa Beta and MAPK pathways to inhibit both virus replication and inflammatory responses. In summary, PPQ-B has the potential to be developed into a novel anti-IAV drug targeting host EGFR pathway in the future. (C) 2017 Elsevier B.V. All rights reserved.
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