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针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白的单克隆中和抗体

Monoclonal neutralizing antibodies against SARS-COV-2 S protein.

作者信息

Cheng Lin-Dong, Li Ping, Lin Yan-Chen, Hu Hui-Xiu, Zhang Ying, Li Hou-Feng, Huang Jing, Tan Li, Ma Ning, Xia Deng-Yun

机构信息

Graduate School, Hebei North University Zhangjiakou 075000, Hebei, China.

Graduate School, Wannan Medical College Wuhu 241000, Anhui, China.

出版信息

Am J Transl Res. 2024 Feb 15;16(2):681-689. doi: 10.62347/ALXM8429. eCollection 2024.

Abstract

Novel coronavirus pneumonia, also known as coronavirus disease 2019 (COVID-19), is caused by sub-severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) infection. The spike (S) protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptors widely expressed on the surface of human cells leading to life-threatening respiratory infections. A serious hazard to human health is posed by the lack of particular treatment medications for this virus infection. We advocate the creation of high-affinity antibodies using the receptor binding domain (RBD) of S protein as a specific antigenic epitope to develop a drug that can precisely target therapy COVID-19 because SARS-CoV-2 infection of the host cells is dependent on S protein binding to ACE2. Finally, we obtained high-affinity antibodies 14F4HL and 14E3HL that have high affinity with RBD and well-drug-forming properties, suitable for further humanization studies. Thus, monoclonal antibodies that neutralize the S protein were identified in our study, which may provide new insights for the development of COVID-19 therapeutic drugs.

摘要

新型冠状病毒肺炎,也称为2019冠状病毒病(COVID-19),是由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染引起的。SARS-CoV-2的刺突(S)蛋白与广泛表达于人类细胞表面的血管紧张素转换酶2(ACE2)受体结合,导致危及生命的呼吸道感染。这种病毒感染缺乏特效治疗药物,对人类健康构成严重危害。我们主张以S蛋白的受体结合域(RBD)作为特异性抗原表位,制备高亲和力抗体,开发能够精准靶向治疗COVID-19的药物,因为SARS-CoV-2感染宿主细胞依赖于S蛋白与ACE2的结合。最终,我们获得了与RBD具有高亲和力且成药性能良好的高亲和力抗体14F4HL和14E3HL,适合进一步进行人源化研究。因此,我们的研究中鉴定出了中和S蛋白的单克隆抗体,这可能为COVID-19治疗药物的开发提供新的思路。

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