Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine
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DOI:
10.1038/s41423-020-0400-4
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发表时间:
2020-03-19
影响因子:
24.1
通讯作者:
Du, Lanying
Du, Lanying
中科院分区:
医学1区
文献类型:
--
作者:
Tai, Wanbo;He, Lei;Du, Lanying

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2019冠状病毒病(COVID-19)的爆发对全球公共卫生构成了严重威胁,要求开发安全有效的预防和治疗方法,以防止其病原体严重急性呼吸综合征冠状病毒2 (SARS-CoV-2),也称为2019新型冠状病毒(2019- ncov)的感染。冠状病毒刺突(S)蛋白在病毒附着、融合和侵入中起着最重要的作用,并作为抗体、侵入抑制剂和疫苗开发的靶标。本研究鉴定了SARS-CoV-2 S蛋白的受体结合域(RBD),发现RBD蛋白与人和蝙蝠血管紧张素转换酶2 (ACE2)受体结合强烈。SARS-CoV-2 RBD对ACE2受体的结合亲和力明显高于SARS-CoV RBD,可以阻断SARS-CoV-2 RBD和SARS-CoV RBD与表达ACE2的细胞的结合和附着,从而抑制它们对宿主细胞的感染。SARS-CoV RBD特异性抗体可与SARS-CoV-2 RBD蛋白交叉反应,SARS-CoV RBD诱导的抗血清可交叉中和SARS-CoV-2,提示开发基于SARS-CoV RBD的疫苗预防SARS-CoV-2和SARS-CoV感染的潜力。
The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.