Hepatology: Pevonedistat一种乙型肝炎病毒的有效抑制剂

2019-04-20 不详 MedSci原创

乙型肝炎病毒(HBV)感染是全世界主要的健康问题。为了预防HBV相关死亡,消除病毒蛋白被认为是HBV治疗的最终目标; 然而,目前可用的核苷(t)ide类似物很少实现这一目标,因为其并没有阻止来自附加型病毒共价闭合环状DNA(cccDNA)的病毒转录。

      乙型肝炎病毒(HBV)感染是全世界主要的健康问题。为了预防HBV相关死亡,消除病毒蛋白被认为是HBV治疗的最终目标; 然而,目前可用的核苷(t)ide类似物很少实现这一目标,因为其并没有阻止来自附加型病毒共价闭合环状DNA(cccDNA)的病毒转录。
 
      最近有研究发现HBV调节蛋白X靶向染色体5/6(Smc5 / 6)的蛋白质结构很独特,用于泛素化和DDB1-CUL4-ROC1 E3连接酶的降解,导致cccDNA的病毒转录增强。这种遍在蛋白依赖性蛋白酶体途径需要额外的泛素样蛋白激活即神经元前体细胞表达的发育下调蛋白8(NEDD8),在本项研究中,研究人员发明出一种NEDD8活化酶抑制剂(pevonedistat),作为抗病毒剂能有效地起作用。试验结果表明Pevonedistat显着恢复了Smc5 / 6蛋白水平,并抑制了HBV小环系统中的病毒转录和蛋白质产生。
 
      结论:pevonedistat是治疗慢性HBV感染的一种很有前景的新型药物。

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    2019-11-22 jklm09
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    2020-01-14 feather89
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  7. [GetPortalCommentsPageByObjectIdResponse(id=2012988, encodeId=6aee201298808, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Fri Oct 25 07:59:00 CST 2019, time=2019-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1825690, encodeId=c06718256907f, content=<a href='/topic/show?id=1a942339426' target=_blank style='color:#2F92EE;'>#乙型肝炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23394, encryptionId=1a942339426, topicName=乙型肝炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Sat Nov 23 09:59:00 CST 2019, time=2019-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2061160, encodeId=8cdc2061160a3, content=<a href='/topic/show?id=ccfa6061407' target=_blank style='color:#2F92EE;'>#有效抑制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60614, encryptionId=ccfa6061407, topicName=有效抑制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=69cb413, createdName=chengjn, createdTime=Thu Oct 24 07:59:00 CST 2019, time=2019-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851971, encodeId=d94418519e1a7, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Nov 22 11:59:00 CST 2019, time=2019-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727969, encodeId=d8f91e279699c, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Tue Jan 14 12:59:00 CST 2020, time=2020-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351558, encodeId=99951351558fd, content=<a href='/topic/show?id=74672339e92' target=_blank style='color:#2F92EE;'>#乙型肝炎病毒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23397, encryptionId=74672339e92, topicName=乙型肝炎病毒)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Mon Apr 22 06:59:00 CST 2019, time=2019-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1427324, encodeId=fb5e142e32450, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Mon Apr 22 06:59:00 CST 2019, time=2019-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=364974, encodeId=b65b3649e4e8, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160304/IMG56D94856B1B5D6405.jpg, createdBy=27931687771, createdName=一个字-牛, createdTime=Sat Apr 20 16:50:24 CST 2019, time=2019-04-20, status=1, ipAttribution=)]
    2019-04-22 gwc384
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    2019-04-20 一个字-牛

    学习了谢谢分享

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众所周知,慢性乙型肝炎病毒感染是我国最为重要的公共卫生问题之一。乙型肝炎病毒共价闭合环状 DNA(cccDNA)是病毒进入细胞后首先形成的产物,在肝细胞核内可形成微小染色体,作为HBV复制的中心,对乙型肝炎病毒的复制以及持续感染状态的建立具有十分重要的意义。

Nat Commun:揭示HBV慢性感染导致肝癌发生的机制

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Digest Dis Sci: HBV相关肝癌根治后的抗病毒治疗可降低肿瘤复发

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