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Cell reports:老药新用— —抗真菌药物伊曲康唑抑制肠道病毒复制

来源:生物谷 2015-02-02 11:12

                                           

2015年2月2日讯 /生物谷BIOON/ --近日,来自荷兰的研究人员在国际期刊cell reports在线发表了他们一项最新研究成果。他们通过研究发现抗真菌抗肿瘤药物伊曲康唑(ITZ)可作为广谱性肠道病毒抑制剂发挥作用。这项研究对开发伊曲康唑在治疗肠道病毒性疾病方面的新作用具有重要意义。
 
文章指出,ITZ能够通过靶向氧化固醇结合蛋白(OSBP)和OSBP相关蛋白4(ORP4)抑制病毒RNA复制,并且发现OSBP/ORP4特异性拮抗剂OSW-1也能够抑制肠道病毒的复制。通过实验证明,敲低OSBP表达能够抑制肠道病毒复制,过表达OSBP或这ORP4能够抵消ITZ和OSW-1对病毒复制的抑制作用。ITZ能够结合OSBP并抑制其发挥胆固醇和4-磷酸磷脂酰肌醇转运功能,可能扰乱了病毒诱导的膜改变,这对病毒复制过程中细胞器形成具有重要影响,同时,研究人员还发现ITZ也能够抑制肝炎C病毒复制。
 
综上所述,研究人员通过实验发现伊曲康唑除具有抗真菌抗肿瘤特性,还可作为广谱性肠道病毒抑制剂发挥作用。这对开发伊曲康唑在治疗肠道病毒性疾病方面的作用具有重要意义。(生物谷Bioon.com)
 
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Itraconazole Inhibits Enterovirus Replication by Targeting the Oxysterol-Binding Protein
 
Jeroen R.P.M. Strating, Lonneke van der Linden, Lucian Albulescu, Joelle Bigay,Minetaro Arita, Leen Delang, Pieter Leyssen, Hilde M. van der Schaar, Kjerstin H.W. Lanke,Hendrik Jan Thibaut, Rachel Ulferts1, , Guillaume Drin, Nina Schlinck, Richard W. Wubbolts, Navdar Sever, Sarah A. Head, Jun O. Liu, Philip A. Beachy, Maria A. De Matteis, Matthew D. Shair,Vesa M. Olkkonen, Johan Neyts, Frank J.M. van Kuppeveld
 
Itraconazole (ITZ) is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.
 
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