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不同种属ACE2蛋白,谁才是病毒的结合之王?

2020-05-12 16:39    浏览量:1172



SARS-CoV-2病毒通过刺突蛋白(S)上的受体结合域(RBD)与宿主细胞受体血管紧张素转化酶2(ACE2)结合,介导冠状病毒进入并感染宿主细胞。


普通哺乳动物中ACE2基因在DNA和肽水平上都高度保守,哺乳动物物种可能是SARS-CoV-2的潜在宿主。最新研究[1]发现ACE2基因在12种常见哺乳动物中均有表达,其中人为SARS-CoV-2的主要宿主;老鼠是常用实验动物模型;蝙蝠和穿山甲分别被认为是SARS-CoV-2的疑似宿主或中间宿主;猫、狗、雪貂和仓鼠是与人接触频繁的宠物;牛、猪、兔和山羊是常见的牲畜。此外,ACE2也在SARS的重要宿主-果子狸(Paguma larvata)体内表达[2]。尽管ACE2在老鼠体内有表达,但小鼠ACE2基因在任何类型肺细胞中均未表达,只在舌头与皮肤中表达,据此推断哺乳动物中ACE2蛋白表达模式可能是存在物种特异性的,另外啮齿类动物模型如大鼠小鼠可能不适合SARS-CoV-2研究。ACE2的接触表面显示出对病毒识别至关重要的氨基酸残基,这些关键残基的变异可能会调节跨物种的感染敏感性。根据序列比对,Mouse和Rat ACE2 与Human ACE2相比有7个关键位点不同,这可能是导致Mouse和Rat ACE2蛋白与SARS-CoV-2 RBD蛋白结合阴性的原因。


研究报道与人类有较多接触机会的狗ACE2基因表达集中于皮肤与眼角膜,且表达水平较高,因此狗可能对SARS-CoV-2感染高度敏感。而且,在ACE2系统发育树中,狗都比其他哺乳动物更接近人类 (Fig. 1),表明这些宠物对冠状病毒的潜在亲和力更高,更适合作为COVID-19肺炎动物模型[1]

Fig.1 ACE2基因的保守性分析


与啮齿类动物相反,序列比对显示猴(Cynomolgus)ACE2与Human ACE2的关键位点同源性一致,且感染研究表明,感染SARS-CoV-2病毒的恒河猴会出现类似COVID-19的症状。ACRO开发的Cyno ACE2(AC2-C52H7)经验证与SARS-CoV-2 S1蛋白和S RBD蛋白均有很好的结合活性,也印证了Cyno ACE2与Human ACE2呈现高度同源性[3]。综上,猴或狗更适合作为COVID-19研究用的模型动物。




ELISA验证

果子狸(Paguma larvata)作为SARS病毒的重要宿主,其体内的ACE2受体蛋白也显示与SARS-CoV-2的S蛋白有结合活性,但结合活性相比人和食蟹猴ACE2与S蛋白结合活性有显著差异。ELISA binding assay验证结果显示果子狸ACE2 与SARS-CoV-2 S1蛋白和S RBD蛋白结合活性(EC50) 分别为52nM、67nM,而食蟹猴ACE2与SARS-CoV-2 S1蛋白和S RBD蛋白结合活性分别达到0.1nM、0.02nM,人与SARS-CoV-2 S1蛋白和S RBD蛋白结合活性分别达到1.15nM、1.16nM。






BLI验证

BLI技术对Human、Cyno、Paguma larvata ACE2蛋白与SARS-CoV-2 S RBD蛋白的结合亲和力进行了验证,Human和Cyno ACE2蛋白与RBD蛋白的结合活性明显高于Paguma larvata。





SPR验证

SPR验证Paguma larvata ACE2蛋白对SARS的结合亲和力要高于SARS-COV-2。SARS S RBD与果子狸ACE2亲和力常数能达到0.101 µM,而SARS-CoV-2 S RBD蛋白与果子狸ACE2亲和力常数只有29 µM。SARS S1蛋白与果子狸ACE2亲和力常数能达到0.796 µM,而SARS-CoV-2 S1蛋白与果子狸ACE2亲和力常数只有47.3 µM。





ACROBiosystems已成功开发了Cyno、Rat、Mouse、Paguma larvata、Human的ACE2蛋白。经BLI验证Cyno ACE2蛋白与SARS-CoV-2 S1 和RBD蛋白的结合活性与文献水平一致[4],可应用于抗SARS-CoV-2的相关研究中。




产品列表


kits  For research use only.
Molecule Cat. No. Species Product Description Protocol/Order
S protein RBD EP-105 SARS-CoV-2 SARS-CoV-2 Inhibitor Screening Kit

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S1 protein MBS-K001 SARS-CoV-2 SARS-CoV-2 Spike S1 protein-coupled magnetic beads

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S protein RBD MBS-K002 SARS-CoV-2 SARS-CoV-2 Spike protein RBD-coupled magnetic beads

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TAS-K003 SARS-CoV-2 Anti-SARS-CoV-2 neutralizing antibody titer serologic assay kit

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S1 protein SP-12 SARS-CoV-2 SARS-CoV2 Spike S1 protein-Coated Plates, Clear, 96-Well

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S protein RBD RP-13 SARS-CoV-2 SARS-CoV2 Spike protein RBD-Coated Plates, Clear, 96-Well

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S1 protein TAS-K001 SARS-CoV-2 SARS-CoV-2 antibody titer assay kit (Spike protein S1)

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S protein RBD TAS-K002 SARS-CoV-2 SARS-CoV-2 antibody titer assay kit (Spike protein RBD)

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Antibody
Molecule Cat. No. Species Product Description Protocol/Order
S protein RBD SAD-S35 Human Anti-SARS-CoV-2 neutralizing antibody (Human IgG1)

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Proteins
Molecule Cat. No. Species Host Product Description Protocol/Order
ACE2 AC2-H82E6 Human HEK293 Biotinylated Human ACE2 / ACEH Protein, His,Avitag™ (MALS verified)

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AC2-H82F9 Human HEK293 Biotinylated Human ACE2 / ACEH Protein, Fc,Avitag™

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AC2-H5257 Human HEK293 Human ACE2 / ACEH Protein, Fc Tag (MALS verified)

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AC2-C52H7 Cynomolgus HEK293 Cynomolgus ACE2 / ACEH Protein, His Tag

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AC2-H52H8 Human HEK293 Human ACE2 / ACEH Protein, His Tag (MALS verified)

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AC2-R5246 Rat HEK293 Rat ACE2 / ACEH Protein, His Tag (MALS verified)

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AC2-M5248 Mouse HEK293 Mouse ACE2 / ACEH Protein, His Tag (MALS verified)

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AC2-P5248 Paguma larvata HEK293 Paguma larvata ACE2 / ACEH Protein, His Tag

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S protein SPN-C52H4 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein (R683A, R685A), His Tag

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SPN-C52H8 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein (R683A, R685A) , His Tag, active trimer (MALS verified)

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SPN-S52H5 SARS HEK293 SARS S protein (R667A), His Tag

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S1 protein S1N-C52H3 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein, His Tag

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S1N-C82E8 SARS-CoV-2 HEK293 Biotinylated SARS-CoV-2 (COVID-19) S1 protein, His,Avitag™ (MALS verified)

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S1N-S52H5 SARS HEK293 SARS S1 protein, His Tag (MALS verified)

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S1N-C52H4 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein, His Tag (MALS verified)

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S1N-C5255 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein, Fc Tag

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S1N-C5257 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein, Mouse IgG2a Fc Tag

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S protein RBD SPD-C82E9 SARS-CoV-2 HEK293 Biotinylated SARS-CoV-2 (COVID-19) S protein RBD, His,Avitag™ (MALS verified)

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SPD-C5255 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD, Fc Tag (MALS verified)

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SPD-S52H6 SARS HEK293 SARS S protein RBD, His Tag (MALS verified)

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SPD-C52H3 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD, His Tag (MALS verified)

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SPD-C5259 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD, Mouse IgG2a Fc Tag

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SPD-S52H4 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (V367F), His Tag

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SPD-S52H5 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (N354D), His Tag

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SPD-S52H7 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (W436R), His Tag

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SPD-S52H8 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (R408I), His Tag

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SPD-S52H3 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (N354D, D364Y), His Tag

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Nucleocapsid protein NUN-C51H9 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) Nucleocapsid protein, His Tag

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NUN-C5227 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) Nucleocapsid protein, His Tag

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NUN-C81Q6 SARS-CoV-2 E.coli Biotinylated SARS-CoV-2 (COVID-19) Nucleocapsid protein, His,Avitag™

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Envelope protein ENN-C5128 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) Envelope protein, His Tag

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Papain-like Protease PAE-C5148 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) Papain-like Protease Protein, His Tag

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NSP1 NS1-C51H7 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP1 Protein, His Tag

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NSP7 NS7-C51H6 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP7 Protein, His Tag

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NSP8 NS8-C5149 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP8 Protein, His Tag

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NSP7 & NSP8 NS8-C5125 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP7&NSP8 Protein, His Tag

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S1 protein S1N-C5256 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein (D614G), His Tag

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预计上线时间:6月5日

SIN-V52H3 HCoV-NL63 HEK293 HCoV-NL63 S1 protein, His Tag

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SIN-V52H4 HCoV-229E HEK293 HCoV-229E S1 protein, His Tag

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SIN-V52H5 HCoV-OC43 HEK293 HCoV-OC43 S1 protein, His Tag

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SIN-V52H6 HCoV-HKU1(isolate N5) HEK293 HCoV-HKU1(isolate N5) S1 protein, His Tag

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S1 protein CTD S1D-C52H3 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein CTD, His Tag

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S1 protein NTD S1D-C52H6 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S1 protein NTD, His Tag

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S protein RBD SPD-C52H4 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (G476S), His Tag

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SPD-C52H5 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S protein RBD (V483A), His Tag

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S2 protein S2N-C5253 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S2 protein, Fc Tag

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预计上线时间:6月4日

S2N-C5254 SARS-CoV-2 HEK293 SARS-CoV-2 (COVID-19) S2 protein, Mouse IgG2a Fc Tag

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Envelope protein ENN-C51P3 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) Envelope protein, His,BBP Tag

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预计上线时间:6月12日

NSP15 NS5-C5145 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP15 Protein, His Tag

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NSP16 & NSP10 NS0-C51W3 SARS-CoV-2 E.coli SARS-CoV-2 (COVID-19) NSP16&NSP10 Heterodimer Protein, His Tag&Twin Strep Tag

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预计上线时间:6月1日




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更多新冠病毒蛋白和检测试剂盒信息请点击文尾阅读原文查看



如果您对此产品感兴趣或有技术问题,欢迎您通过下方信息联系:

(上文中ELISA/SPR/BLI数据也都可通过下方信息联系我们申请Protocol)

邮件:order.cn@acrobiosystems.com

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Reference:

[1] Sun et al., 2020 Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2, doi: https://doi.org/10.1101/2020.03.30.015644.

[2] Stawiski et al., 2020 Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility. doi: https://doi.org/10.1101/2020.04.07.024752.

3] Melin et al., 2020 Comparative ACE2 variation and primate COVID-19 risk, https://doi.org/10.1101/2020.04.09.034967.

4) Wrapp et al., 2020 Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. DOI: 10.1126/science. Abb 2507.



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