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Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation
Antiviral Research ( IF 7.6 ) Pub Date : 2018-02-03 , DOI: 10.1016/j.antiviral.2018.01.012
Seong-Ryeol Kim , Jae-Hyoung Song , Jae-Hee Ahn , Geun-Shik Lee , Huijeong Ahn , Sung-il Yoon , Seung Goo Kang , Pyeung-Hyeun Kim , Sang-Min Jeon , Eun-Ji Choi , Sooyoung Shin , Younggil Cha , Sungchan Cho , Dong-eun Kim , Sun-Young Chang , Hyun-Jeong Ko

Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor. Intranasal administration of budesonide lowered the pulmonary HRV load and the levels of IL-1β cytokine leading to decreased lung inflammation. Budesonide regulates IL-1β production following HRV infection independent of inflammasome activation. Instead, budesonide induces mitochondrial reactive oxygen species followed by activation of autophagy. Further, the inhibition of autophagy following chloroquine or bafilomycin A1 treatment reduced the anti-viral effect of budesonide against HRV, suggesting that the antiviral activity of budesonide was mediated via autophagy. The results suggest that budesonide represents a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection.



中文翻译:

布地奈德对通过自噬激活介导的人鼻病毒感染的抗病毒和抗炎活性

人鼻病毒(HRV)感染引起所有普通感冒的80%以上,并且与哮喘和慢性阻塞性肺疾病的严重并发症相关。为了鉴定抗HRV感染的抗病毒药物,我们筛选了800种FDA批准的药物,发现布地奈德是可能的候选药物之一。布地奈德是一种皮质类固醇,通常用于预防哮喘加重和普通感冒症状。布地奈德可特异性保护宿主细胞免受HRV感染后的细胞毒性,这取决于糖皮质激素受体的表达。鼻内给予布地奈德可降低肺部HRV负荷和IL-1β细胞因子水平,从而减少肺部炎症。布地奈德独立于炎症小体激活,调节HRV感染后的IL-1β产生。反而,布地奈德诱导线粒体活性氧,然后激活自噬。此外,在氯喹或bafilomycin A1处理后对自噬的抑制作用降低了布地奈德对HRV的抗病毒作用,表明布地奈德的抗病毒活性是通过自噬介导的。结果表明布地奈德代表了一种有前景的抗病毒和抗炎药候选物,可用于治疗人类鼻病毒感染。

更新日期:2018-02-03
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