球探足球比分直播

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瑞德西韦化合物及其作用位点RDRP酶的相关分析

来源:中国知识产权网     发布时间:2020-02-17     点击量:
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  前言

  2YUE4RI,LAIZIMEIGUOSHENGWUGONGSIJILIDEDEYAOWURUIDEXIWEI(Remdesivir)DIDAZHONGGUO,JIANGYOUZHONGRIYOUHAOYIYUANHUXIYUWEIZHONGYIXUEKEZHURENCAOBINJIAOSHOUQIANTOUDUIWUHAN270MINGHUANZHEJINXINGLINCHUANGSHIYAN,YIBIANJINYIBUQUEDINGQIDUI2019-nCoVDEGONGXIAO。

  BENWENDUIRUIDEXIWEIHUAHEWUJIQIZUOYONGWEIDIANRDRPMEIJINXINGXIANGGUANFENXI,BINGFUSHANGLERUIDEXIWEIHUAHEWUYONGYUZHILIAOGUANZHUANGBINGDUDEZHUANLIWO2017049060LIMIANHANGAIDEHUAHEWUJIEGOUSHIBIAODAN,GONGZHUWEIYANJIURENYUANHEZHISHICHANQUANJIANSUORENYUANCANKAO。

  病毒序列暂无太多位点变异

  2019-nCov,ZHEIYICHUANKANQILAIHAOWUGUANLIANDESHUZIHEZIMUZUHEZAIYIQIJIUSHIYINQI2019NIANMOZHI2020NIANCHUCICIYIQINGDEZUIKUIHUOSHOU。2020NIAN1YUE11RI,SHANGHAIFUDANDAXUESHENGWUYIXUEYANJIUYUANYUFUDANDAXUEFUSHUSHANGHAIGONGGONGWEISHENGLINCHUANGZHONGXINZHANGYONGZHENJIAOSHOUYANJIUTUANDUIDIYISHIJIANGONGKAILEGAIBINGDUDEQUANJIYINZUXULIE,SUIHOULAIZIZHONGGUOJIBINGYUFANGKONGZHIZHONGXIN、WUHANBINGDUXUEYANJIUSUOHEZHONGGUOYIXUEKEXUEYUANDE5GEEWAI2019-nCoVXULIEYETIJIAOZHIGSAIDSHUJUKUYIGONGQUANQIUKEYANGONGZUOZHEJINXINGXIANGGUANFENXI。

  现共有43个数据递交单位交付的92个病毒株共97条病毒序列在国家生物信息中心(CNCB)/国家基因组科学数据中心(NGDC)公开(http://bigd.big.ac.cn/ncov#progress),从上传序列上看,2019-nCoV同SARS-Cov和Bat-SL-CoVZC45这两个已知冠状病毒的整体序列相似度分别达80.12%和88.17%,而根据最新研究(中国科学院武汉病毒研究所石正丽团队发表于Nature的最新报道),该种病毒同来源自云南的蝙蝠SARS相关病毒样本(BetaCoV/bat/Yunnan/RaTG13/2013)同源性更高,可达96.16%,并且再次明确2019-nCov的受体同SARS-Cov一致,均为ACE2。

  采集自不同样本的2019-nCov菌株之间相似度较高,均在99.9%以上,可见截止到现在我们所采样获得的病毒基因序列间尚未产生太多位点的变异。

Figure 1. BUTONGYANGBENJIANJIYINXULIEDEXIANGSIDUBIDUI

  “人民的希望”

  瑞德西韦化合物专利布局

  2019-nCoVZUOWEIRNABINGDU,BENSHENJUYOUFANZHISULVGAO、KEBIANXINGQIANGDENGTEDIAN,DAOZHIZHENDUIQIDETEXIAOYAOWUJIYIMIAODEYANFAHUANMAN。RUHEJINKUAIDIKONGZHIYIQINGXUNZHAOXIANGGUANDEZHILIAOFANGAN,“LAOYAOXINYONG”SHIZUIWEIKUAIJIEFANGBIANDETUJING,TEBIESHICONGYIJINGWANCHENGLINCHUANGSHIYANHUOZHESHANGSHIYAOWUZHONGSHAIXUANDAOJUYOUKANG2019-nCoVBINGDU,ZHILIAOXINXINGGUANZHUANGBINGDUFEIYANNCPDEGONGNENGCHANPIN。2YUE4RI,LAIZIMEIGUOSHENGWUGONGSIJILIDEDEYAOWURUIDEXIWEI(Remdesivir)DIDAZHONGGUO,JIANGYOUZHONGRIYOUHAOYIYUANHUXIYUWEIZHONGYIXUEKEZHURENCAOBINJIAOSHOUQIANTOUDUIWUHAN270MINGHUANZHEJINXINGLINCHUANGSHIYAN,YIBIANJINYIBUQUEDINGQIDUI2019-nCoVDEGONGXIAO。

球探足球比分直播  RUIDEXIWEISHIJILIDEGONGSIZAIYANFADAIHAOWEIGS-441524DEKANGRNABINGDUXIAOFENZIHUAHEWUSHANGJINYIBUFANYINGSHENGCHENG。GS-441524SHIHEGANLEISIWU,YI“JINGZHENGXINGYIZHIJI”DEJIAOSERAOLUANBINGDUFUZHIGUOCHENG。ERZAICIJICHUSHANGCHANSHENGDERUIDEXIWEIWEIPIAOLINGHEGANSUANQIANTIYAOWU,YUANYANFAMUDEZAIYUZHILIAOAIBOLABINGDUGANRAN,QIZUOYONGJIZHIZAIYUXINGCHENGHUOXINGSANLINSUANXINGSHITONGATPJINGZHENGCONGERYIZHIRNAYILAIDERNAJUHEMEI(RNA-Dependent RNA polymerase,RDRP)HUOXING。

  TONGGUOCASHAO1809249-37-3HUOZHEZHIJIEYIRemdesivirMINGCHENGZAIPatbaseDEChemical ExploreNEIJINXINGQUEDINGJIEGOUCHAXUN(BUXIANDINGQISHOUXINGJIEGOU),JIANGHUODESUOYOUKENENGXINGJIEGOUJINXINGZHUANLIJIANSUO,KEFAXIANJILIDEZI2011NIANQIJIUGAIHUAHEWUJIEGOUZAIQUANQIUFANWEINEI(SHEJI48GEGUOJIA)GONGSHENQING166PIANXIANGGUANZHUANLIFENBUYU7GEZHUANLIJIAZUZHONG,QIZHONGJINYOU3GEZHUANLIJIAZUZHONGHANYOUSHOUQUANZHUANLI。

球探足球比分直播Figure 2. YIRemdesivirHUAXUEJIEGOUJINXINGJIANSUO,

BAOHANJIANSUOQIBUTONGSHOUXINGJIEGOUDEHUAHEWU

球探足球比分直播  CONGXIATUKEJIAN,JILIDEYU2011NIANQIDUIRUIDEXIWEIHUAHEWUJINXINGZHUANLISHENQING,ZAI2015NIANDADAOGAOFENGQI,DANGNIANSHENQINGXIANGGUANZHUANLI57JIAN,DIERGEGAOFENGQIZEZAI2018NIAN,JIAIBOLAYIQINGFASHENGSHIQI。XIANGXINZAICICIYIQINGZHIHOU,DUIYURUIDEXIWEIZAIXINGUANBINGDUDEZHILIAOYONGTUFANGMIANHUIYOUGENGDUODEZHUANLIJINXINGSHENQING。

Figure 3. (A) JILIDEGONGSIJIUZHEIYIHUAHEWUJINXINGZHUANLISHENQINGDENIANFENFENBU

(B)RUIDEXIWEIHUAHEWU2010NIANZHI2020NIANZHUANLISHENQINGJISHOUQUANZHUANGKUANG

(C)XIANGGUANZHUANLISHENQING、YOUXIANQUAN、SHOUQUANDENGDESHIJIANKUADU

  ZHEI7GEZHUANLIJIAZUFENBIECONGHUAHEWUBENSHEN、ZHIBEIFANGFA、ZHILIAOYONGTU、JINGXINGDENGFANGMIANDUIRUIDEXIWEIHUAHEWUJINXINGBAOHU。ZUIZAODUIYUHUAHEWUJIEGOUJINXINGGONGKAIDEZHUANLIYINGGAIWEIWO2012012776(WO2011US45102),QIDUIYINGDEZHONGGUOTONGZUZHUANLIWEICN103052631(CN201180035776)。ZHEIPIANZHUANLITIGONGLEYONGYUTONGGUOSHIYONGSHI(I)DEHEGAN、QIHEGANLINSUANYANHUOZHIHEQIANYAOLAIZHILIAOFUNIANBINGDUKEBINGDUGANRANDEFANGFA。ZAIGAIZUZHUANLIZHONG,GAIHUAHEWUJIEGOUSHIRUTUSANSUOSHICHUXIANZAIQUANLIYAOQIU13ZHONG。

球探足球比分直播Figure 4. RUIDEXIWEIHUAHEWUZAIZHUANLIZHONGCHUXIANWEIZHI

  SUIHOU,JILIDEYU2015NIANJIUGAIHUAHEWUSHENQINGLEZHIBEIYONGYUZHILIAOSIZHUANGBINGDUKE(Filoviridae)BINGDUGANRANDEHUAHEWUHEYAOWUZUHEWUDEFANGFA(WO2016069826),BINGZAIQIZHONGZHICHUSUOTIGONGDEHUAHEWU、ZUHEWUHEFANGFATEBIESHIYONGYUZHILIAOMAERBAOBINGDU、AIBOLABINGDUHEWANQUBINGDU。GAIHUAHEWUJIEGOUYECHUXIANZAIQIDUIYINGDETONGZUZHUANLIDESHISHILIZHONG。SUIHOUYU2016NIANHE2017NIANFENBIESHENQINGLERUIDEXIWEIDUIBUTONGBINGDUGANRANDEZHILIAOFANGFA。

  2016年申请该化合物在治疗沙粒病毒科(Arenaviridaea)和冠状病毒科感染的相关专利(WO2017049060球探足球比分直播),在该专利的权利要求中列举了化合物通式,并在权利要求64-74中描述了该化合物对冠状病毒,包括SARS, MERS, 229E, NL63, OC43以及HKUI病毒的治疗。2017年申请了该化合物在治疗黄病毒科病毒感染的方法(WO2017184668)。

Figure 5. WO17049060ZHUANLIZHONGGUANYUGUANZHUANGBINGDUZHILIAOXIANGGUANDEQUANLIYAOQIUJIHUAHEWUJIEGOUSHI

  XIANGAIZUZHUANLIZAIZHONG、MEI、RI、HANDEFALVZHUANGTAIRUTUSUOSHI,QIZAIMEIGUOYISHOUQUAN,ZAIRIBENHEHANGUOCHUYUWUXIAOZHUANGTAI,ZHONGGUOXIANGGUANZHUANLICHUYUGONGKAIJIEDUAN。

球探足球比分直播Figure 6. ZHUANLIZUZAIZHONGMEIRIHANDEFALVZHUANGTAIQINGKUANG

  CHUCIZHIWAI,JILIDEGONGSIHAIYU2018NIANSHENQINGBAOHURUIDEXIWEIHUAHEWUDEXINXINGYANHEJIEJINGXINGSHI(WO2018204198),BINGYUTONGNIANSHENQINGLEZUHEWU(RUIDEXIWEIHUAHEWU、HUANHUJINGYIJIKEXUANZEDEpHDIAOJIEJI)ZHUANLI,YONGYUZHILIAOBINGDUGANRAN(WO2019014247),RUIDEXIWEIHUAHEWUJIEGOUZAISHANGSHULIANGJIANZHUANLIZHONGJUNZAIDULIQUANLIYAOQIUZHONGCHUXIAN。

Figure 7. RUIDEXIWEIJIEGOUCHUXIANZAILIANGPIANZHUANLIDEDULIQUANLIYAOQIUZHONG

  抑制瑞德西韦作用位点RDRP酶活性的相关方法和专利

  RUQIANSHU,RUIDEXIWEIDEZUOYONGWEIDIANSHIZUOWEIJINGZHENGJIYIZHIRDRPGONGNENG,RDRPZUOWEIRNABINGDUFUZHISUOXUDEGUANJIANMEI,TONGGUOYIZHIQIHUOXINGYINGXIANGBINGDUFUZHICONGERDADAOYIZHIBINGDUDEZHILIAOFANGFAZAIYIWANGDEKEXUEYANJIUZHONGYEYOUGUODUOZHONGXIANGGUANDESHIYANYUFANGAN。SUIRANCONGJILISHANGKANFULIANDANGURNABINGDURUFUNIANBINGDUKEHESIZHUANGBINGDUKE,YOUYUQIFUZHIXUYAOXIANHECHENGHUBUZHENGLIANDETESHUXING,DUIYURDRPDEYILAIXINGJIAOQIANG,DANRDRPDUIYUZHENGLIANDANGURNABINGDURUSARSDENGYEJUYOUZHONGYAOZUOYONG。SUOYIWOMENYEKEYIKAOLVCONGZHENGLIANHEFULIANRNABINGDUDERDRPXIANGGUANYANJIUZHONGZHAOXUNLEISIDEYANJIUFANGANYONGZUOJIEJIAN。

球探足球比分直播  WOMENSHIYONGRNABINGDU(ZHENGLIAN、FULIAN)、GUANZHUANGBINGDUHERDRP/SPIKEZUOWEIGUANJIANCI,TONGSHIXIANDINGIPCFENLEIHAOWEIAHUOZHEC,ZAIPatbaseSHUJUKUZHONGJINXINGJIANSUO。

  我们共发现39个相关专利家族,涵盖多个方面,包括同瑞德西韦一样对RDRP酶起抑制作用的核苷类似物或磷酸酯、重组RNA病毒疫苗、应用反义核苷酸或RNA干扰抑制酶活,以及利用短链RNA对病毒进行快速检测的方法。

球探足球比分直播  YINWEIMEIGEBINGDUZHONGDERDRPCHABIEJIAODA,ZAIYIWANGJIAOWEICHENGSHUDERNABINGDUYANJIUZHONGZHUYAOYIZHENDUIBINGGANBINGDUDERDRPMEINS5BDEXIANGGUANYIZHIHUAHEWUYANJIUJIAODUO,RUMOKEHEIONISZHIYAOGONGSI(YUANISISZHIYAOGONGSI)GONGTONGSHENQINGDEWO2002057425ZEZHIXIANGYIZHONGYILAIYURNABINGDUJUHEWUYIZHIJIDEHEGANHUAHEWUJIMOUXIEYANSHENGWU。ERWO2011130557ZHONGZETIGONGYIZHONGJUYOUJIANGDIDUXINGHEZENGQIANGKANGBINGDUHUOXINGDEWUHUANHEGANLINSUANZHIHUAHEWUJIQIYAOXUESHANGJIESHOUDEYANHERONGJIHUAWU,YONGYUYIZHIBINGDURNAYILAIXINGRNAJUHEMEI、YIZHIBINGDUNIZHUANLUMEI、YIZHIBAOKUOBINGGANHUORENFANZHUANLUBINGDUDEFUZHIDENG。

球探足球比分直播  CHUQUFENZIHUAHEWUDUIRDRPMEIJINXINGHUOXINGYIZHIWAI,HAIYOUYILEICHANGJIANDEMEIHUOYIZHIFANGFA,LIYONGDUANLIANRNA(BAOKUOSHUANGLIANRNAHUOZHEFANYIHEGANSUAN)DUIBAXIANGXULIEJINXINGHUOXINGYIZHI。

球探足球比分直播  WEILEGENGZHUNQUEZHAOXUNDAOHECICI2019-nCoVDERDRPJIYINXULIEGENGWEIXIANGGUANDEDUANLIANRNAXULIE,WOMENSHIYONGGenBankSHANGTIGONGDERDRPBUFENXULIE(MN975265.1)ZAIGenomeQuestSHANGJINXINGJIANSUO,YIXULIEPIPEIDU80%YISHANGHEGUANZHUANGBINGDU/SARS/MERSZUOWEIXIANDINGTIAOJIAN,BAOKUO18GEZHUANLIJIAZUZHONGDE46GEXIANGGUANZHUANLI,ZHUYAOFENBUZAIZHENDUAN、RNAGANRAODENGFANGMIAN,RUIONISSHENGWUZHIYAOGONGSIDESHOUQUANZHUANLIUS7339051TIJIYONGFANYIGUAJUHEGANSUANZHILIAOHUXIXITONGJIBING,TIGONGLEYIZHONGGUAJUHUAHEWUHEZUHEWUDESHEJIHEHECHENG,YONGYUJIANGDITINEIHUOTIWAISARSBINGDUHUOXING,YUFANGHUOZHILIAOSARSBINGDUXIANGGUANJIBING。

  MEIGUOALILAMUZHIYAO(Alnylam)YEZAICILINGYUJINXINGGUOYANJIU,ERZHONGGUOYIYAOYANFAGONGSIRUHANGZHOUXINRUIJIASHENGWUYIYAOJISHUKAIFAYOUXIANGONGSIHEBEIJINGSANNUOJIAYISHENGWUJISHUYOUXIANZERENGONGSI(BEIJINGSHUTAISHENZHIYAOGONGSIDEYANFAZIGONGSI)DOUSHENQINGGUOXIANGGUANZHUANLI。

球探足球比分直播Figure 8 GUANZHUANGBINGDURDRPXULIEJIANSUODEXIANGGUANJIEGUOLIEBIAO

球探足球比分直播  YISHANGJINWEIDUIRUIDEXIWEIHUAHEWUJIQIZUOYONGWEIDIANRDRPMEIDEXIANGGUANFENXI。

  数据库使用

  为了让更多的科研人员拥有更多工具和数据库对新冠病毒情况进行分析,我们特意为相关科研和知识产权人员开放全球专利及化学结构检索数据库Patbase和生物序列检索数据库GenomeQuest的免费试用账号,诸位可通过邮件联系后获取相关账号。

  WOMENXIWANGYOUGENGDUODEKEYANRENYUANNENGGOUJINKUAIHUODEZUIWEIXIANGGUANDESHUJU,WEIDAYINGZHEICHANGZHAN“YI”ZHENGQUDAOGENGDUODESHIJIAN,HUANYINGDAJIAJIUXIANGGUANYITIJINXINGTANTAO。

  联系邮箱:zhaolina@cnipr.com(请注明您的单位邮箱、姓名和所在单位)

  Patbase化学结构检索界面:

  GenomeQuest专利及非专利序列检索界面(包含专门的2019-nCov序列库):

  本文的最后,附上瑞德西韦化合物用于治疗冠状病毒的专利WO2017049060里面涵盖的化合物结构式EXCEL表单球探足球比分直播(识别小程序下载),供诸位研究人员和知识产权检索人员参考。

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