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Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response
Ma, LL (Ma, Lin-Lin); Wang, HQ (Wang, Hui-Qiang); Wu, P (Wu, Ping); Hu, J (Hu, Jin); Yin, JQ (Yin, Jin-Qiu); Wu, S (Wu, Shuo); Ge, M (Ge, Miao); Sun, WF (Sun, Wen-Fang); Zhao, JY (Zhao, Jiang-Yu); Aisa, HA (Aisa, Haji Akber); Li, YH (Li, Yu-Huan); Jiang, JD (Jiang, Jian-Doug)
2016
Source PublicationFREE RADICAL BIOLOGY AND MEDICINE
ISSN0891-5849
Volume96Issue:7Pages:347-361
Abstract

Given the limitation of available antiviral drugs and vaccines, there remains to be a pressing need for novel anti-influenza drugs. Rupestonic acid derivatives were reported to have an anti-influenza virus activity, but their mechanism remains to be elucidated. Herein, we aim to evaluate the antiviral activity of YZH-106, a rupestonic acid derivative, against a broad-spectrum of influenza viruses and to dissect its antiviral mechanisms. Our results demonstrated that YZH-106 exhibited a broad-spectrum antiviral activity against influenza viruses, including drug-resistant strains in vitro. Furthermore, YZH-106 provided partial protection of the mice to Influenza A virus (IAV) infection, as judged by decreased viral load in lungs, improved lung pathology, reduced body weight loss and partial survival benefits. Mechanistically, YZH-106 induced p38 MAPK and ERK1/2 phosphorylation, which led to the activation of erythroid 2-related factor 2 (Nrf2) that up-regulated heme oxygenase-1 (HO-1) expression in addition to other genes. HO-1 inhibited IAV replication by activation of type I IFN expression and subsequent induction of IFN-stimulated genes (ISGs), possibly in a HO-1 enzymatic activity independent manner. These results suggest that YZH-106 inhibits IAV by up-regulating HO-1-mediated IFN response. HO-1 is thus a promising host target for antiviral therapeutics against influenza and other viral infectious diseases.

KeywordRupestonic Acid Derivative Influenza Virus Heme Oxygenase-1 Type i Interferon
DOI10.1016/j.freeradbiomed.2016.04.021
Indexed BySCI
WOS IDWOS:000377619600031
Citation statistics
Document Type期刊论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/4653
Collection资源化学研究室
Affiliation1.Chinese Acad Med Sci, Inst Med Biotechnol, Beijing Key Lab Antiinfect Agents, Beijing 100050, Peoples R China
2.Peking Union Med Coll, Beijing 100050, Peoples R China
3.Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China
4.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang 830011, Peoples R China
Recommended Citation
GB/T 7714
Ma, LL ,Wang, HQ ,Wu, P ,et al. Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response[J]. FREE RADICAL BIOLOGY AND MEDICINE,2016,96(7):347-361.
APA Ma, LL .,Wang, HQ .,Wu, P .,Hu, J .,Yin, JQ .,...&Jiang, JD .(2016).Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response.FREE RADICAL BIOLOGY AND MEDICINE,96(7),347-361.
MLA Ma, LL ,et al."Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response".FREE RADICAL BIOLOGY AND MEDICINE 96.7(2016):347-361.
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