Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants.

Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants.
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对最近出现的 SARS-CoV-2 变体受体结合的分子见解

DOI:
10.1038/s41467-021-26401-w
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发表时间:
2021-10-20
影响因子:
16.6
通讯作者:
Qi J
Qi J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Han P;Su C;Zhang Y;Bai C;Zheng A;Qiao C;Wang Q;Niu S;Chen Q;Zhang Y;Li W;Liao H;Li J;Zhang Z;Cho H;Yang M;Rong X;Hu Y;Huang N;Yan J;Wang Q;Zhao X;Gao GF;Qi J

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出现了多种SARS-CoV-2变种病毒(VOCs),其中一些与全球病例数量的增加有关。然而,目前对人血管紧张素转换酶2(HACE2)受体与这些VOCs相互作用的分子基础还缺乏了解。在这里,我们研究了几种VOCs,包括Alpha,Beta和Gamma,并证明了五种变体的受体结合结构域(RBD)增加了与hACE2的结合亲和力,四种变体的伪病毒增加了进入敏感细胞的能力。HACE2-RBD复合体的晶体结构有助于识别促进hACE2结合亲和力变化的关键残基。此外,可溶性hACE2蛋白能有效地预防大多数变种假病毒。我们的发现提供了重要的分子信息,并可能有助于开发针对这些新出现的突变的新型治疗和预防药物。
Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
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期刊: Science (New York, N.Y.)
影响因子: --
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DOI: 10.1107/s0907444904019158
发表时间: 2004-12-01
影响因子: 2.2
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