High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme.
High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme.
复制标题
高亲和力纳米抗体阻断SARS-CoV-2刺突受体结合域与人血管紧张素转换酶的相互作用。
DOI：
10.1038/s41598-020-79036-0
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发表时间：
2020-12-22
影响因子：
4.6
通讯作者：
Brody DL
中科院分区：
文献类型：
--
作者：
Esparza TJ;Martin NP;Anderson GP;Goldman ER;Brody DL
目前，针对导致COVID-19大流行的SARS-CoV-2病毒，几乎没有获得批准的有效治疗方法。纳米体是12-15 kDa的单域抗体片段，可以通过吸入输送，与其他生物制剂相比，相对便宜的大规模生产。我们已经分离出与SARS-CoV-2刺突蛋白受体结合域结合的纳米体，并以1-5 nM的亲和力阻断刺突蛋白与血管紧张素转换酶2 （ACE2）的相互作用。主要候选纳米体NIH-CoVnb-112可阻断SARS-CoV-2刺突假型慢病毒感染表达人ACE2的HEK293细胞，EC50为0.3µg/mL。NIH-CoVnb-112在雾化后保持结构完整性和效力。此外，NIH-CoVnb-112阻断ACE2与几种高亲和力刺突蛋白变体之间的相互作用。这些纳米体及其衍生物具有治疗、预防和诊断的潜力。
There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12–15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1–5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
11.4
作者：
Li, WH;Zhang, CS;Sui, JH;Kuhn, JH;Moore, MJ;Luo, SW;Wong, SK;Huang, IC;Xu, KM;Vasilieva, N;Murakami, A;He, YQ;Marasco, WA;Guan, Y;Choe, HY;Farzan, M
通讯作者：
Farzan, M
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
158.5
作者：
Scully, M.;Cataland, S. R.;Zeldin, R. K.
通讯作者：
Zeldin, R. K.
影响因子：
8
作者：
Dumoulin, M;Conrath, K;Matagne, A
通讯作者：
Matagne, A