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新型冠状病毒肺炎抗体疗法综述

Review of COVID-19 Antibody Therapies.

作者信息

Chen Jiahui, Gao Kaifu, Wang Rui, Nguyen Duc Duy, Wei Guo-Wei

出版信息

ArXiv. 2020 Jun 18:arXiv:2006.10584v1.

PMID:32601601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7316097/
Abstract

Under the global health emergency caused by coronavirus disease 2019 (COVID-19), efficient and specific therapies are urgently needed. Compared with traditional small-molecular drugs, antibody therapies are relatively easy to develop and as specific as vaccines in targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and thus attract much attention in the past few months. This work reviews seven existing antibodies for SARS-CoV-2 spike (S) protein with three-dimensional (3D) structures deposited in the Protein Data Bank. Five antibody structures associated with SARS-CoV are evaluated for their potential in neutralizing SARS-CoV-2. The interactions of these antibodies with the S protein receptor-binding domain (RBD) are compared with those of angiotensin-converting enzyme 2 (ACE2) and RBD complexes. Due to the orders of magnitude in the discrepancies of experimental binding affinities, we introduce topological data analysis (TDA), a variety of network models, and deep learning to analyze the binding strength and therapeutic potential of the aforementioned fourteen antibody-antigen complexes. The current COVID-19 antibody clinical trials, which are not limited to the S protein target, are also reviewed.

摘要

在2019冠状病毒病(COVID-19)引发的全球卫生紧急状况下,迫切需要高效且特异的疗法。与传统小分子药物相比,抗体疗法相对易于研发,并且在靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)方面与疫苗一样具有特异性,因此在过去几个月备受关注。这项工作综述了七种针对SARS-CoV-2刺突(S)蛋白且其三维(3D)结构已存入蛋白质数据库的现有抗体。评估了五种与严重急性呼吸综合征冠状病毒(SARS-CoV)相关的抗体结构对SARS-CoV-2的中和潜力。将这些抗体与S蛋白受体结合域(RBD)的相互作用与血管紧张素转换酶2(ACE2)和RBD复合物的相互作用进行了比较。由于实验结合亲和力差异达几个数量级,我们引入拓扑数据分析(TDA)、多种网络模型以及深度学习来分析上述十四种抗体-抗原复合物的结合强度和治疗潜力。本文还综述了当前不限于S蛋白靶点的COVID-19抗体临床试验。