MERS-CoV spike protein: a key target for antivirals.
MERS-CoV spike protein: a key target for antivirals.
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DOI：
10.1080/14728222.2017.1271415
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发表时间：
2017-02
影响因子：
5.8
通讯作者：
Jiang S
中科院分区：
文献类型：
--
作者：
Du L;Yang Y;Zhou Y;Lu L;Li F;Jiang S
中东呼吸综合征（MERS）的持续威胁突出了开发有效的抗病毒治疗方法以预防和治疗MERS冠状病毒（MERS-CoV）感染的重要性。一种表面刺突（S）蛋白通过与细胞受体二肽基肽酶-4（DPP 4）结合，然后在病毒和宿主细胞膜之间融合，引导MERS-CoV进入宿主细胞。MERS-CoV S蛋白是开发阻断病毒进入和抑制膜融合的治疗方法的关键靶点。本文综述了MERS-CoV S蛋白的结构和功能，特别是S1受体结合结构域（RBD）和S2七肽重复序列1（HR 1）作为治疗靶点的研究进展，重点介绍了中和性单克隆抗体（mAb）和抗病毒肽的研究进展。没有抗MERS-CoV治疗药物被批准用于人类。几种靶向S的中和mAb和肽已证明对MERS-CoV感染有效，为开发提供了可行性。通常，靶向RBD的人中和mAb比靶向S蛋白其他区域的人中和mAb更有效。然而，逃逸突变体病毒的出现和mAb的局限性使得有必要将识别不同中和表位的中和mAb组合并以提高的功效和降低的成本对其进行工程改造。预期肽序列的优化将产生具有改进效力的下一代抗MERS-CoV肽。
The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. This review illustrates MERS-CoV S protein’s structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb’s limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.