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战疫时刻|SARS-CoV-2入侵人体潜在靶点汇总(收藏)

发布时间:2020-04-13 10:47 |  点击次数:

自2019年底新型冠状病毒肺炎(COVID19)爆发以来,截至到2020年3月26日,全球感染人数已超过46万,死亡人数也已超过2万。这次疫情的爆发给全球的经济造成了不可估量的损失,同时也让人们的生活陷入了一片混乱。SARS-CoV-2是导致COVID19呼吸系统疾病的病原体。了解更多SARS-CoV-2,目前既没有抗病毒的特效药,也没有预防的疫苗。而且不幸的是,科学界对SARS-CoV-2感染的分子细节知之甚少。


目前针对于SARS-CoV-2入侵人体的主流说法是,刺突蛋白(spike,S)是介导病毒入侵宿主细胞的关键蛋白。SARS-CoV-2是通过S蛋白找到宿主细胞受体与之结合,通过网格蛋白介导膜融合被内吞入细胞。而且宿主细胞与病毒表面蛋白配受体关系和亲和力决定了病毒的传染性和嗜细胞特性,而致病力与其侵入的宿主细胞类型及其功能相关。有关于SARS-CoV-2入侵人体的靶点,目前有最新研究支撑的是ACE2和CD147。

SARS-CoV-2入侵人体靶点研究现状

1、ACE2

目前SARS-CoV-2入侵人体门户靶点公认度最高的是血管紧张素转化酶2(ACE2)。2020年1月,科学家们通过晶体结构解析证实ACE2是SARS-CoV-2 S蛋白的受体,而且ACE2与新冠病毒的RBD(受体结合结构域)之间的亲和力,比其与SARS病毒的RBD的亲和力高10到20倍,这也是SARS-CoV-2超强感染性的原因。新冠病毒S蛋白以三聚体形态存在,每一个单体中约有1300多个氨基酸,其中300多个氨基酸构成了“受体结合结构域”(RBD),即S蛋白与ACE2相联结的地方 [1] [2] [3]了解更多ACE2,请戳 >>

但是ACE2通常仅表达于心、肾、血管内皮细胞,而COVID-19患者通常是呼吸道、消化道、肝、脾多器官受损,鼻咽拭子、唾液、尿液、粪便和血液均检出病毒核酸,这提示SARS-CoV-2在人体还有其他受体。
 

2、CD147

在严重急性呼吸器官综合征(SARS)冠状病毒入侵宿主细胞过程中,CD147分子可通过与CyPA的相互作用介导与其在HIV-1入侵中类似的作用机制。而CD147-拮抗肽9与HEK293细胞的结合率高,对SARS-CoV具有抑制作用。由于SARS-CoV-2与SARS-CoV具有相似的特征,陈志南研究团队对CD147在SARS-CoV-2侵袭宿主细胞中的可能作用进行了研究。并于2020年3月14日,在预印版平台BioRxiv上发表了题为“SARS-CoV-2 invades host cells via a novel route: CD147-spike protein”的文章。该实验结果表明,在宿主细胞上阻断CD147对新冠病毒具有抑制作用,而且CD147在促进该病毒对宿主细胞的侵袭中起重要作用。另外,表面等离子体共振分析则证实了CD147和S蛋白(SP)的相互作用[4]了解更多CD147,请戳 >>


3、其他靶点

尽管CD147可以在多个组织和器官中表达,比如恶性肿瘤、中枢神经、表皮细胞基底层、毛囊外根鞘细胞、精子头部、血液系统、消化系统及泌尿系统,可以参与肿瘤发生发展、组织重建、淋巴细胞应答、精子发生、病毒感染和发育早期神经系统功能调节。那这是不是意味着SARS-CoV-2入侵人体是不是就没有其他靶点了呢?

为了验证这一点,2020年3月22日,David E. Gordon等94位专家在生物学预印本期刊在线发表了一篇通过新冠病毒SARS-CoV-2蛋白与人蛋白相互作用筛选潜在治疗靶点的文章。文章作者来自加州大学旧金山分校(美国新冠病毒研究的重要中心之一)等多个单位,题目为“A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing”。

其实文章的思路很简单,但工作量极为庞大。研究人员在人类细胞中克隆、标记和表达了SARS-CoV-2的29个蛋白中的26个,并通过亲和纯化质谱法(AP-MS)鉴定了与每一种蛋白相互作用的人蛋白。共鉴定出332种高度可信的与病毒蛋白相互作用的人蛋白(PPIs),其中66个可以作为潜在靶点,这些蛋白可由69种现有FDA批准的药物、临床试验中的药物和/或临床前化合物靶向。宿主依赖因子介导病毒感染的鉴定可能为开发广泛有效的针对SARS-CoV-2和其他致命冠状病毒株的抗病毒治疗提供重要的分子靶点[5]
 

SARS-CoV-2蛋白及互作靶点一览表

SARS-CoV-2分离株的序列分析表明,该30kb基因组编码多达14个开放阅读框(Orfs)。5端的Orf1a / Orf1ab开放阅读框可编码多蛋白,这些蛋白会被蛋白水解处理成16个非结构蛋白(Nsp1-16),形成复制酶/转录酶复合物(RTC)。RTC由多种酶组成,包括Nsp3、Nsp5,Nsp7-Nsp8 复合物、Nsp12、Nsp13、Nsp14、Nsp15以及Nsp10 / Nsp16。在病毒基因组的3末端,从9个预测的亚基因组RNA中表达了多达13个Orf。这些包括四个结构蛋白:S、E、M和N,以及九种假定的辅助因子。在基因组成上,SARS-CoV-2基因组与SARS-CoV非常相似:每个都有一个Orf1ab编码16个预测的Nsps,每个都有四个典型的冠状病毒结构蛋白。但是,它们的3开放阅读框互补性不同:SARS-CoV-2具有Orf3b和Orf10,其Orf8是完整的,而SARS-CoV编码的是Orf8a和Orf8b [6] [7] [8]

下表中的26个SARS-CoV-2蛋白分别为:Nsp1、Nsp2、Nsp4、Nsp5、Nsp6、Nsp7、Nsp8、Nsp9、Nsp10、Nsp11、Nsp12、Nsp13、Nsp14、Nsp15、Spike (S)、E、N、M、Orf3a、Orf3b、Orf6、Orf7a、Orf8、Orf9b、Orf9c和Orf10,另外还有一个突变体Nsp C145A。
 

SARS-CoV Proteins Human Potential Interactome Targets
Nsp1 COLGALT1, PKP2, POLA1, POLA2, PRIM1, PRIM2
Nsp2 EIF4E2, FKBP15, GIGYF2POR, RAP1GDS1, SLC27A2, WASHC4
Nsp4 ALG11, DNAJC11, IDE, NUP210, TIMM10, TIMM10B, TIMM29, TIMM9
Nsp5 HDAC2
Nsp5 C145A TRMT1, GPX1
Nsp6 ATP13A3, ATP5MG, ATP6AP1, SIGMAR1
Nsp7 ACSL3, AGPS, COMT, CYB5B, CYB5R3, DCAKD, DNAJC19, FAM162A, GNB1, GNG5, HS2ST1, LMAN2, MOGS, MTARC1, NAT14, NDUFAF2, PTGES2, QSOX2, RAB10, RAB14, RAB18RAB1ARAB2ARAB5C, RAB7A, RAB8A, RALA, RHOASCARB1, SCCPDH, SELENOS, TOR1AIP1
Nsp8 AATF, ATE1, CCDC86, DDX10, EXOSC2, EXOSC3, EXOSC5, EXOSC8, HECTD1, LARP7, MEPCE, MPHOSPH10, MRPS2, MRPS25, MRPS27, MRPS5, NARS2, NGDN, NOL10, NSD , NSD2, SEPSECSSRP19SRP54, SRP72
Nsp9 DCAF7, EIF4H, FBLN5, FBN1, FBN2, GTF2F2, MAT2B, MIB1, NEK9, NUP214, NUP54, NUP58, EIF4H, NUP62, NUP88, SPART, ZNF503
Nsp10 AP2A2, AP2M1, ERGIC1, GFERGRPEL1
Nsp11 TBCA
Nsp12 AKAP8, BCKDK, CRTC3, LARP4B, MYCBP2, PDZD11, PLEKHA5, PPIL3, PRRC2B, RBM41, RIPK1, SBNO1, SLU7, TCF12, TYSND1, UBAP2, UBAP2L, USP54, ZC3H7A, ZNF318
Nsp13 AKAP9, C1orf50, CDK5RAP2, CENPF, CEP112, CEP135, CEP250, CEP350, CEP43, CEP68, CIT, CLIP4, CNTRL, ERC1, FYCO1, GCC1, GCC2, GOLGA2, GOLGA3, GOLGB1, GORASP1, GRIPAP1, HOOK1, HSBP1, JAKMIP1, MIPOL1, NIN, NINL , PCNTPDE4DIPPRKACA, PRKAR2A, PRKAR2B, RDX, TBK1, TBKBP1, TLE1, TLE3, TLE5, USP13
Nsp14 GLA, IMPDH2, SIRT5
Nsp15 ARF6NUTF2RNF41
Spike GOLGA7, ZDHHC5
Orf3a ALG5, ARL6IP6, CLCC1, HMOX1, SUN2, TRIM59, VPS11, VPS39
Orf3b STOML2
E AP3B1, BRD2, BRD4, CWC27, SLC44A2, ZC3H18
N CSNK2A2CSNK2B, DDX21, FAM98A, G3BP1, G3BP2, LARP1, MOV10, PABPC1PABPC4, RBM28, RPL36, RRP9, SNIP1, UPF1
M AAR2, AASS, ACADM, AKAP8L, ANO6, ATP1B1, ATP6V1A, BZW2, COQ8B, ETFA, FAM8A1, FASTKD5, GGCX, INTS4, PITRM1, PMPCA, PMPCB, PSMD8, REEP5, REEP6, RTN4, SAAL1, SLC25A21, SLC30A7, SLC30A9, STOMTARS2, TUBGCP2, TUBGCP3, YIF1A
Orf6 MTCH1, NUP98, RAE1
Orf7a HEATR3, MDN1
Orf8 ADAM9, ADAMTS1, CHPF, CHPF2, CISD3, COL6A1, DNMT1, EDEM3, EMC1, ERLEC1, ERO1B, ERP44, FBXL12, FKBP10, FKBP7, FOXRED2, GDF15, GGH, HS6ST2, HYOU1, IL17RA, INHBE, ITGB1LOXMFGE8NEU1, NGLY1, NPC2, NPTX1, OS9, PCSK6, PLATPLD3PLEKHF2PLOD2, POFUT1, POGLUT2, POGLUT3, PUSL1, PVRSDF2, SIL1, SMOC1, STC2, TM2D3, TOR1A, UGGT2
Orf9b BAG5CHMP2A, CSDE1, DCTPP1, DPH5, MARK1, MARK2, MARK3, PTBP2, SLC9A3R1, TOMM70
Orf9c ABCC1, ACAD9, ALG8, BCS1L, DPY19L1, ECSIT, ERMP1, F2RL1, FAR2, GHITM, GPAA1, NDFIP2, NDUFAF1, NDUFB9, NLRX1, PIGO, PIGS, RETREG3, SCAP, SLC30A6, TAPT1, TMED5, TMEM39B, TMEM97, UBXN8, WFS1
Orf10 CUL2, ELOBELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, ZYG11B



332新冠入侵人体潜在靶点产品目录

  • 部分蛋白产品
靶点 货号 种属 来源 表达区域 标签
AATF  CSB-RP052644h Human E.coli 6-294aa N-terminal GST-tagged
ABCC1 CSB-EP001056HU Human E.coli 1248-1531aa N-terminal 6xHis-tagged
ACADM CSB-EP001126HU Human E.coli 26-421aa N-terminal 6xHis-tagged
AP2M1 CSB-EP001872HU Human E.coli 1-435aa N-terminal 6xHis-SUMO-tagged
ARF6 CSB-EP001996HU Human E.coli 1-175aa N-terminal 6xHis-SUMO-tagged
BAG5 CSB-EP890743HU Human E.coli 1-447aa N-terminal 6xHis-SUMO-tagged
BZW2 CSB-EP896544HU Human E.coli 1-419aa N-terminal GST-tagged
CENPF CSB-BP005210HU Human Baculovirus 1759-2093aa N-terminal MBP-tagged and C-terminal 6xHis-tagged
           
 
  • 部分抗体产品
产品名称 产品货号 种属 种属反应性 应用
AAR2 Antibody CSB-PA896704LA01HU Human Human ELISA, IHC
AASS Antibody CSB-PA883373LA01HU Human Human ELISA, WB, IHC
AATF Antibody CSB-PA05264A0Rb Human Human ELISA, IHC
ACAD9 Antibody CSB-PA887999ESR1HU Human Human ELISA, WB, IHC
ACADM Antibody CSB-PA001126LA01HU Human Human ELISA, IHC
ADAM9 Antibody CSB-PA618774ESR1HU Human Human ELISA, WB, IHC
ADCK4 Antibody CSB-PA839305LA01HU Human Human ELISA, WB, IHC, IF
AES Antibody CSB-PA001405ESR2HU Human Human ELISA, IHC
AGPS Antibody CSB-PA001457LA01HU Human Human ELISA, WB, IHC, IF
AKAP8L Antibody CSB-PA892152ESR1HU Human Human ELISA, IHC
AKAP9 Antibody CSB-PA857882LA01HU Human Human ELISA, WB, IHC, IF
ALG11 Antibody CSB-PA647192LA01HU Human Human ELISA, IHC, IF
ALG5 Antibody CSB-PA896924LA01HU Human Human ELISA, IHC
ANO6 Antibody CSB-PA679761LA01HU Human Human ELISA, IF
AP2A2 Antibody CSB-PA001870DSR2HU Human Human, Mouse ELISA, WB, IHC
AP2M1 Antibody CSB-PA00625A0Rb Human Human ELISA, WB, IHC
AP3B1 Antibody CSB-PA001874ESR1HU Human Human ELISA, IHC
ARF6 Antibody CSB-PA001996LA01HU Human Human ELISA, WB, IHC
ATE1 Antibody CSB-PA002268LA01HU Human Human ELISA, IHC, IF
ATP1B1 Antibody CSB-PA002326LA01HU Human Human, Rat, Mouse ELISA, WB, IHC, IF
ATP5L Antibody CSB-PA002374LA01HU Human Human ELISA, IHC
BAG5 Antibody CSB-PA890743HA01HU Human Human, Mouse ELISA, WB, IHC
BCKDK Antibody CSB-PA002607ESR2HU Human Human ELISA, WB, IHC
BCS1L Antibody CSB-PA897463ESR1HU Human Human ELISA, WB, IHC
BRD4 Antibody CSB-PA002802LA01HU Human Human ELISA, IF
CDK5RAP2 Antibody CSB-PA847226LA01HU Human Human ELISA, IHC, IF
CEP135 Antibody CSB-PA721063LA01HU Human Human ELISA, IF
CEP250 Antibody CSB-PA871581LA01HU Human Human ELISA, IF
CEP68 Antibody CSB-PA765741LA01HU Human Human ELISA
CHMP2A Antibody CSB-PA04524A0Rb Human Human ELISA, WB, IHC
CLCC1 Antibody CSB-PA857024LA01HU Human Human ELISA, WB, IHC, IF, IP
CRTC3 Antibody CSB-PA747623LA01HU Human Human ELISA, IHC
CSDE1 Antibody CSB-PA006040LA01HU Human Human ELISA, IHC, IF
CSNK2A2 Antibody CSB-PA526319HA01HU Human Human ELISA, IHC, IF
CSNK2B Antibody CSB-PA01655A0Rb Human Human ELISA, IHC
CUL2 Antibody CSB-PA623822LA01HU Human Human ELISA, WB, IHC
CYB5B Antibody CSB-PA006310LA01HU Human Human, Mouse ELISA, WB, IHC, IF
CYB5R3 Antibody CSB-PA02655A0Rb Human Human ELISA, WB, IHC, IF
DCAF7 Antibody CSB-PA026056ESR2HU Human Human ELISA, IHC
DCAKD Antibody CSB-PA855481LA01HU Human Human ELISA
DNAJC19 Antibody CSB-PA853400ESR1HU Human Human, Mouse ELISA, WB, IHC, IP
DNMT1 Antibody CSB-PA007082HA01HU Human Human ELISA, IHC, IF
DPH5 Antibody CSB-PA862001LA01HU Human Human ELISA, IHC, IF
DPY19L1 Antibody CSB-PA23079A0Rb Human Human ELISA, IF
ECSIT Antibody CSB-PA859414ESR2HU Human Human ELISA, WB, IHC
EIF4E2 Antibody CSB-PA007558ESR1HU Human Human ELISA, IHC
ELOB Antibody CSB-PA620878ESR1HU Human Human ELISA, WB, IHC
         
 
  • 部分ELISA试剂盒
靶点 产品货号 种属 样本类型 检测范围
ADAM9 CSB-E11904h Human serum, plasma, tissue homogenates, cell culture supernates, ascitic fluid 62.5 pg/mL-4000 pg/mL
BCS1L CSB-EL002644HU Human serum, plasma, tissue homogenates, cell lysates 7.8 pg/mL-500 pg/mL
BRD4 CSB-EL002802HU Human serum, plasma, tissue homogenates 18.75 pg/mL-1200 pg/mL
COL6A1 CSB-E16375h Human serum, plasma, cell culture supernates, urine 31.25 pg/mL-2000 pg/mL
DNAJC19 CSB-EL007026HU Human serum, plasma, tissue homogenates, cell lysates 28 pg/mL-1800 pg/mL
FBLN5 CSB-EL008454HU Human serum, plasma, cell culture supernates, tissue homogenates 62.5 pg/mL-4000 pg/mL
FBN1 CSB-E13141h Human serum, plasma, tissue homogenates 78 pg/mL-5000 pg/mL
FBN2 CSB-EL008457HU Human serum, plasma, tissue homogenates 0.625 ng/mL-40 ng/mL
GDF15 CSB-E12009h Human serum, plasma, tissue homogenates, urine 7.8 pg/mL-500 pg/mL
GFER  CSB-EL009370HU Human serum, plasma, tissue homogenates, cell lysates 18.75 pg/mL-1200 pg/mL
GGH CSB-EL009389HU Human serum, plasma, tissue homogenates, cell lysates 0.45 ng/mL-30 ng/mL
GLA CSB-E09457h Human serum, plasma, tissue homogenates 7.8 pg/mL-500 pg/mL
GPX1 CSB-EL009866HU Human serum, plasma, tissue homogenates 15.6 μU/mL-1000 μU/mL
HMOX1 CSB-E08266h Human serum, plasma, tissue homogenates 15.6 ng/mL-1000 ng/mL
IL17RA CSB-EL011602HU Human serum, plasma, tissue homogenates, cell lysates 78 pg/mL-5000 pg/mL
IMPDH2 CSB-E17855h Human serum, plasma, cell culture supernates, tissue homogenates 23.5 pg/mL-1500 pg/mL
ITGB1 CSB-EL011880HU Human serum, plasma, tissue homogenates 62.5 pg/mL-4000 pg/mL
LOX CSB-E16376h Human serum, plasma, tissue homogenates 0.625 ng/mL-40 ng/mL
MFGE8 CSB-E12637h Human serum, cell culture supernates, urine, cerebrospinal fluid (CSF) 781.25 pg/mL-50000 pg/mL
NEU1 CSB-E13811h Human serum, urine, cerebrospinal fluid (CSF) 0.312 ng/mL-20 ng/mL
NPC2 CSB-EL015976HU Human serum, plasma, tissue homogenates, cell lysates 0.312 ng/mL-20 ng/mL
 


>>下载332新冠入侵人体潜在靶点产品目录


相关阅读:

新冠肺炎|COVID-19细胞因子风暴

战疫时刻|Th17细胞分化


ACE2—新型冠状病毒入侵人体的靶标

战疫时刻|CD147—另一个新冠病毒入侵的关键靶点

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  • 酶联免疫试剂盒 食品安全及药物残留酶联免疫试剂盒 食品安全及药物残留酶联免疫试剂盒