A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein
A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein
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DOI：
10.1128/jvi.00433-14
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发表时间：
2014-06-01
影响因子：
5.4
通讯作者：
Zhou, Yusen
中科院分区：
文献类型：
--
作者：
Du, Lanying;Zhao, Guangyu;Zhou, Yusen
迫切需要预防和治疗战略，以防治新出现的中东呼吸综合征冠状病毒（MERS-CoV）引起的感染。在这里，我们开发了一种中和性单克隆抗体（MAb），命名为Mersmab 1，它可以有效地阻止MERS-CoV进入人类细胞。生物化学分析显示，Mersmab 1特异性结合MERS-CoV刺突蛋白的受体结合结构域（RBD），从而竞争性阻断RBD与其细胞受体二肽基肽酶4（DPP 4）的结合。此外，RBD的丙氨酸扫描已经鉴定了DPP 4结合表面上的几个残基，这些残基用作Mersmab 1的中和表位。这些结果表明，如果人源化，Mersmab 1可能作为治疗和预防MERS-CoV感染的治疗性抗体发挥作用。此外，Mersmab 1可以促进MERS CoV RBD的构象和抗原性的研究，从而指导MERS CoV亚单位疫苗的合理设计。
Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.