A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection.
A super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection.
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DOI：
10.1038/s41598-021-89957-z
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发表时间：
2021-05-19
影响因子：
4.6
通讯作者：
Rabbitts T
中科院分区：
文献类型：
--
作者：
Miller A;Leach A;Thomas J;McAndrew C;Bentley E;Mattiuzzo G;John L;Mirazimi A;Harris G;Gamage N;Carr S;Ali H;Van Montfort R;Rabbitts T
需要治疗SARS-CoV-2冠状病毒（COVID-19）引起的严重急性呼吸综合征的方法。干扰病毒抗原与血管紧张素转换酶2（ACE-2）受体的相互作用是通过阻断冠状病毒感染人类细胞的有前途的策略。我们已经实施了一种新的蛋白质工程技术，使用来自p53蛋白的自组装四聚化结构域，生产与人免疫球蛋白γ1 Fc区偶联的超强四价形式的ACE 2。这种高分子量Quad蛋白（ACE 2-Fc-TD）保留与SARS-CoV-2受体结合刺突蛋白的结合，并可与刺突蛋白加上抗病毒抗体形成复合物。ACE 2-Fc-TD作为一种强有力的诱饵蛋白，其性能优于可溶性单体和二聚体ACE 2蛋白，并以大大增强的功效阻断SARS-CoV-2假病毒和SARS-CoV-2病毒感染。ACE 2四聚体蛋白复合物有望成为开发抗COVID-19诱饵治疗蛋白的重要因素。与单克隆抗体相比，ACE 2诱饵不太可能受到SARS-CoV-2突变的影响，SARS-CoV-2突变开始以变异形式出现。此外，如果将来出现新的冠状病毒，ACE 2多聚体蛋白将可用作治疗蛋白，因为这些蛋白可能与ACE 2受体相互作用。
Approaches are needed for therapy of the severe acute respiratory syndrome from SARS-CoV-2 coronavirus (COVID-19). Interfering with the interaction of viral antigens with the angiotensin converting enzyme 2 (ACE-2) receptor is a promising strategy by blocking the infection of the coronaviruses into human cells. We have implemented a novel protein engineering technology to produce a super-potent tetravalent form of ACE2, coupled to the human immunoglobulin γ1 Fc region, using a self-assembling, tetramerization domain from p53 protein. This high molecular weight Quad protein (ACE2-Fc-TD) retains binding to the SARS-CoV-2 receptor binding spike protein and can form a complex with the spike protein plus anti-viral antibodies. The ACE2-Fc-TD acts as a powerful decoy protein that out-performs soluble monomeric and dimeric ACE2 proteins and blocks both SARS-CoV-2 pseudovirus and SARS-CoV-2 virus infection with greatly enhanced efficacy. The ACE2 tetrameric protein complex promise to be important for development as decoy therapeutic proteins against COVID-19. In contrast to monoclonal antibodies, ACE2 decoy is unlikely to be affected by mutations in SARS-CoV-2 that are beginning to appear in variant forms. In addition, ACE2 multimeric proteins will be available as therapeutic proteins should new coronaviruses appear in the future because these are likely to interact with ACE2 receptor.
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影响因子：
4.3
作者：
Hobbs EC;Reid TJ
通讯作者：
Reid TJ
影响因子：
3.4
作者：
Svergun, DI
通讯作者：
Svergun, DI
DOI：
10.1126/science.abc0870
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chan KK;Dorosky D;Sharma P;Abbasi SA;Dye JM;Kranz DM;Herbert AS;Procko E
通讯作者：
Procko E
影响因子：
15.8
作者：
ter Meulen, Jan;van den Brink, Edward N.;Poon, Leo L. M.;Marissen, Wilfred E.;Leung, Cynthia S. W.;Cox, Freek;Cheung, Chung Y.;Bakker, Arjen Q.;Bogaards, Johannes A.;van Deventer, Els;Preiser, Wolfgang;Doerr, Hans Wilhelm;Chow, Vincent T.;de Kruif, John;Peiris, Joseph S. M.;Goudsmit, Jaap
通讯作者：
Goudsmit, Jaap
DOI：
10.1016/s0140-6736(20)32137-1
发表时间：
2020-11-14
期刊：
Lancet (London, England)
影响因子：
--
作者：
Poland GA;Ovsyannikova IG;Kennedy RB
通讯作者：
Kennedy RB