Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
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DOI：
10.3390/v11010031
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发表时间：
2019-01-01
期刊：
影响因子：
4.7
通讯作者：
Jiang, Shibo
中科院分区：
文献类型：
--
作者：
Wang, Cong;Hua, Chen;Jiang, Shibo
中东呼吸综合征冠状病毒(MERS-CoV)一直对全球公共卫生构成威胁，但目前尚无预防或治疗MERS-CoV感染的治疗方法或疫苗。我们以前发现了针对MERS冠状病毒S2蛋白HR1结构域的融合抑制肽(HR2P-M2)和针对S1刺突蛋白受体结合域(RBD)的高效中和单抗(M336)。然而，M336对RBD突变的MERS冠状病毒株的疗效降低，而HR2P-M2的效力较低，因此单独使用时限制了临床应用。然而，我们在此报道，M336和HR2P-M2联合使用在抑制MERS-CoV S蛋白介导的细胞-细胞融合和MERS-CoV假病毒感染方面显示出很强的协同作用，无论是否有RBD突变的MERS-CoV假病毒，导致抗病毒活性的增强。因此，这一组合策略可用于临床对MERS冠状病毒感染患者的紧急治疗。
Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell-cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.