Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma.

Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma.
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DOI:
10.1038/s41598-021-84840-3
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发表时间:
2021-03-10
期刊:
影响因子:
4.6
通讯作者:
Yao ZQ
Yao ZQ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang L;Zhao J;Nguyen LNT;Adkins JL;Schank M;Khanal S;Nguyen LN;Dang X;Cao D;Thakuri BKC;Lu Z;Zhang J;Zhang Y;Wu XY;El Gazzar M;Ning S;Moorman JP;Yao ZQ

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最近的 COVID-19 大流行对全球公共卫生构成了严重威胁,因此迫切需要确定 SARS-CoV-2 刺突 (S) 蛋白介导的病毒进入所涉及的分子机制,这对于预防和/或治疗这种新出现的传染病至关重要。在本研究中,我们使用 SARS-CoV-2-S 转染的 293 T 作为效应细胞和表达 ACE2 的 293 T 作为靶细胞,通过细胞-细胞融合测定检查了人 COVID-19 恢复期血浆的阻断活性。我们证明 SARS-CoV-2 S 蛋白表现出非常高的膜融合能力,并能有效介导病毒融合和进入靶细胞。重要的是,我们发现含有高滴度 IgG 中和抗体的 COVID-19 恢复期血浆可以通过干扰 SARS-CoV-2-S/ACE2 或 SARS-CoV-S/ACE2 相互作用来阻止细胞间融合和病毒进入。这些发现表明,COVID-19 恢复期血浆不仅可以抑制 SARS-CoV-2-S,还可以交叉中和 SARS-CoV-S 介导的膜融合和病毒进入,支持其作为 SARS-CoV-2 以及其他 SARS-CoV 感染的预防和/或治疗剂的潜力。
The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell–cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell–cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.
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