Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV
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SARS-CoV-2 刺突糖蛋白在病毒进入过程中的特征及其与 SARS-CoV 的免疫交叉反应

DOI:
10.1038/s41467-020-15562-9
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发表时间:
2020-03-27
影响因子:
16.6
通讯作者:
Qian, Zhaohui
Qian, Zhaohui
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ou, Xiuyuan;Liu, Yan;Qian, Zhaohui

文献摘要

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自2002年以来,β冠状病毒(CoV)已经引起了三次人畜共患疫情,2002-2003年的SARS-CoV,2012年的MERS-CoV以及2019年底新出现的SARS-CoV-2。然而,目前对SARS-CoV-2的生物学知之甚少。本文利用SARS-CoV-2 S蛋白假病毒系统,证实了人血管紧张素转换酶2(hACE 2)是SARS-CoV-2的受体,发现SARS-CoV-2主要通过内吞进入293/hACE 2细胞,PIKfyve、TPC 2和组织蛋白酶L是进入细胞的关键,SARS-CoV-2 S蛋白的稳定性不如SARS-CoV S蛋白。多克隆抗SARSS 1抗体T62抑制SARS-CoV S的进入,但不抑制SARS-CoV-2S假病毒体。使用SARS和COVID-19患者的血清进行的进一步研究显示,交叉中和作用有限,这表明从一种感染中恢复可能无法保护另一种感染。我们的研究结果为SARS-CoV-2的药物和疫苗的开发提供了潜在的靶点。
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.