新型冠状病毒抗体和小分子抑制剂的研究现状  

The Research Status of Novel Coronavirus Antibodies and Small Molecule Inhibitors

作　　者：武昕 于汉杰 包晓娟 王雨姿 李铮 WU Xin;YU Han-Jie;BAO Xiao-Juan;WANG Yu-Zi;LI Zheng(Laboratory for Functional Glycomics,College of Life Sciences,Northwest University,Xi’an 710069,China)

机构地区：[1]西北大学生命科学学院功能糖组学实验室,西安710069

出　　处：《生物化学与生物物理进展》2024年第4期754-771,共18页Progress In Biochemistry and Biophysics

基　　金：陕西省重点研发计划(2021ZDLSF01-04);陕西省自然科学基础研究计划(2021JM-319)资助项目。

摘　　要：世界卫生组织已宣布新型冠状病毒感染(coronavirus disease 2019,COVID-19)的爆发为全球大流行。中和抗体和小分子抑制剂在预防及治疗COVID-19中发挥重要作用。尽管已开发出了多种中和抗体以及疫苗,但是随着病原体严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)的不断变异,现有的抗体及疫苗面临巨大的挑战。小分子抑制剂主要通过干扰病毒与宿主的结合以及病毒自身的复制达到消灭病毒以及抑制病毒感染的作用,并且对SARS-CoV-2突变株具有广谱抑制作用,是当前研究的热点。近年来国内外学者对SARS-CoV-2的小分子抑制剂做了大量的研究工作,本文根据中和抗体识别的抗原表位以及小分子抑制剂的作用机制分别对用于预防及治疗COVID-19的中和抗体和小分子抑制剂进行综述,讨论其研究现状,并展望小分子抑制剂的应用前景,以期为该领域的进一步研究提供参考。The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19)is a global pandemic.As mutations occurred in the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the global epidemic still needs further concern.Worryingly,the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining.There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection.Neutralizing antibodies play an important role in the prevention and treatment of COVID-19.The interaction of spike-receptor-binding domain(Spike-RBD)of SARS-CoV-2 and human angiotensin-converting enzyme 2(ACE2)is the first and critical step of SARS-CoV-2 infection.Hence,the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development.Evusheld,the combination of Tixagevimab and Cilgavimab monoclonal antibodies(mAbs)targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1,BA.4 and BA.5,which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection.The nucleocapsid(N)protein is a conservative and high-abundance structural protein of SARS-CoV-2.The nCoV396 monoclonal antibody,isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2.This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein.The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G,B.1.1.7,B.1.351,B.1.617.1 and P.1 variants in vitro and in vivo,but did not impact the biological activity of ACE2.Compared with neutralizing antibodies,small molecule inhibitors have several advantages,such as broad-spectrum inhibitory effect,low cost,and simple administration methods.Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain(NTD)of SARS-CoV-2 spike protein.Known drugs such as chlo

关 键 词：新型冠状病毒感染 严重急性呼吸系统综合征冠状病毒2 突变株 中和抗体 小分子抑制剂 

分 类 号：Q5[生物学—生物化学] Q7