科微学术

生物工程学报

2025年5月10日 15:36 星期六
首页 > 过刊浏览>2022年第38卷第9期 >3173-3193. DOI:10.13345/j.cjb.220328
PDF HTML阅读 XML下载 导出引用 引用提醒
新冠病毒中和单克隆抗体及纳米抗体研究进展
作者:
基金项目:

中国科学院战略先导项目（XDB29030104）；福建省自然科学基金（2021J01838）；国家自然科学基金（31870731,31772049）；国家重点研发计划（2018YFD0901004）


SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies:a review
Author:
  • 摘要
    • | |
  • 访问统计
    • |
  • 参考文献 [70]
    • |
  • 相似文献 [20]
    • | | |
  • 文章评论
    摘要:

    由严重急性呼吸系统综合征冠状病毒2型(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)引起的疾病被命名为新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)，是一种具有强传染性、高易感性、长潜伏期的传染病。病毒刺突蛋白受体结合结构域(receptor binding domain,RBD)和细胞血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)之间的相互作用使得SARS-CoV-2顺利进入细胞。本文对SARS-CoV-2与ACE2的相关作用机制进行了简单概述，对目前针对SARS-CoV-2中和单克隆抗体、纳米抗体的最新研究进展进行了总结，探讨了新冠肺炎的发展过程和抗体药物的研究方向，以期为包括新冠肺炎在内的新发、突发传染病中和抗体药物的研发提供参考。

    Abstract:

    Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.

    参考文献
    [1] Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 1975, 256(5517):495-497.
    [2] Corti D, Purcell LA, Snell G, et al. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell, 2021, 184(12):3086-3108.
    [3] Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N Engl J Med, 2021, 384(11):1003-1014.
    [4] Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. Naturally occurring antibodies devoid of light chains. Nature, 1993, 363(6428):446-448.
    [5] Greenberg AS, Avila D, Hughes M, et al. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature, 1995, 374(6518):168-173.
    [6] Muyldermans S. Nanobodies:natural single-domain antibodies. Annu Rev Biochem, 2013, 82:775-797.
    [7] 严昊, 冯建远, 张子仪, 等. 纳米抗体的制备与临床应用研究进展. 中国畜牧兽医, 2021, 48(2):685-694. Yan H, Feng JY, Zhang ZY, et al. Progress in preparation and clinical application of nanobody. Chin Anim Husb Vet Med, 2021, 48(2):685-694(in Chinese).
    [8] Sheng YM, Wang K, Lu QZ, et al. Nanobody- horseradish peroxidase fusion protein as an ultrasensitive probe to detect antibodies against Newcastle disease virus in the immunoassay. J Nanobiotechnology, 2019, 17(1):35.
    [9] Sun ZC, Lv JW, Liu X, et al. Development of a nanobody-AviTag fusion protein and its application in a streptavidin-biotin-amplified enzyme-linked immunosorbent assay for ochratoxin A in cereal. Anal Chem, 2018, 90(17):10628-10634.
    [10] Delfin-Riela T, Rossotti MA, Echaides C, et al. A nanobody-based test for highly sensitive detection of hemoglobin in fecal samples. Anal Bioanal Chem, 2020, 412(2):389-396.
    [11] Muyldermans S. Applications of nanobodies. Annu Rev Anim Biosci, 2021, 9:401-421.
    [12] 陆湛, 符兆胤, 黄志卫, 等. SARS-CoV, MERS-CoV, SARS-CoV-2冠状病毒研究进展. 分子影像学杂志, 2020, 43(1):174-178. Lu Z, Fu ZY, Huang ZW, et al. Research progress of SARS-CoV, MERS-CoV, SARS-CoV-2. J Mol Imaging, 2020, 43(1):174-178(in Chinese).
    [13] Xu XT, Chen P, Wang JF, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci, 2020, 63(3):457-460.
    [14] Wu AP, Peng YS, Huang BY, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe, 2020, 27(3):325-328.
    [15] Dai LP, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol, 2021, 21(2):73-82.
    [16] Chan JFW, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect, 2020, 9(1):221-236.
    [17] Walls AC, Park YJ, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020, 181(2):281-292.e6.
    [18] Du LY, He YX, Zhou YS, et al. The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat Rev Microbiol, 2009, 7(3):226-236.
    [19] Shang J, Wan YS, Luo CM, et al. Cell entry mechanisms of SARS-CoV-2. PNAS, 2020, 117(21):11727-11734.
    [20] Kim MH, Kim HJ, Chang J. Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full- length spike protein of middle east respiratory syndrome coronavirus. PLoS One, 2019, 14(7):e0220196.
    [21] Peng Y, Du N, Lei YQ, et al. Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design. EMBO J, 2020, 39(20):e105938.
    [22] Chen RE, Zhang XW, Case JB, et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat Med, 2021, 27(4):717-726.
    [23] Tegally H, Wilkinson E, Giovanetti M, et al. Detection of a SARS-CoV-2 variant of concern in south Africa. Nature, 2021, 592(7854):438-443.
    [24] Wibmer CK, Ayres F, Hermanus T, et al. SARS-CoV-2501Y.V2 escapes neutralization by south African COVID-19 donor plasma. Nat Med, 2021, 27(4):622-625.
    [25] Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature, 2021, 596(7871):276-280.
    [26] Iketani S, Liu LH, Guo YC, et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature, 2022, 604(7906):553-556.
    [27] Cao YL, Yisimayi A, Jian FC, et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature. 2022, 608(7923):593-602.
    [28] Zhang LZ, Jackson CB, Mou HH, et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun, 2020, 11(1):6013.
    [29] Wan YS, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan:an analysis based on decade-long structural studies of SARS coronavirus. J Virol, 2020, 94(7):e00127- e00120.
    [30] Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with covid-19. N Engl J Med, 2021, 384(3):229-237.
    [31] Jones BE, Brown-Augsburger PL, Corbett KS, et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med, 2021, 13(593):eabf1906.
    [32] Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19:a randomized clinical trial. JAMA, 2021, 325(7):632-644.
    [33] Shi R, Shan C, Duan XM, et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature, 2020, 584(7819):120-124.
    [34] Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, 2020, 369(6506):1014-1018.
    [35] Hansen J, Baum A, Pascal KE, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science, 2020, 369(6506):1010-1014.
    [36] Haskologlu IC, Erdag E, Sayiner S, et al. Melatonin and REGN-CoV2 combination as a vaccine adjuvant for Omicron variant of SARS-CoV-2. Mol Biol Rep, 2022, 49(5):4061-4068.
    [37] Merison T, Goldman A, Bomze D. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med, 2021, 385(20):e70.
    [38] Loo YM, McTamney PM, Arends RH, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med, 2022, 14(635):eabl8124.
    [39] Dong JH, Zost SJ, Greaney AJ, et al. Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol, 2021, 6(10):1233-1244.
    [40] VanBlargan LA, Errico JM, Halfmann PJ, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med, 2022, 28(3):490-495.
    [41] Cathcart AL, Havenar-Daughton C, Lempp FA, et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv, 2021, DOI:10.1101/2021.03.09.434607.
    [42] Kreuzberger N, Hirsch C, Chai KL, et al. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev, 2021:9(9):CD013825.
    [43] Ryu DK, Kang BB, Noh H, et al. The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2. Biochem Biophys Res Commun, 2021, 578:91-96.
    [44] Ryu DK, Song RN, Kim M, et al. Therapeutic effect of CT-P59 against SARS-CoV-2 south African variant. Biochem Biophys Res Commun, 2021, 566:135-140.
    [45] Yuan M, Zhu X, He WT, et al. A broad and potent neutralization epitope in SARS-related coronaviruses. PNAS, 2022, 119(29):e2205784119
    [46] Takashita E, Kinoshita N, Yamayoshi S, et al. Efficacy of antibodies and antiviral drugs against covid-19 Omicron variant. N Engl J Med, 2022, 386(10):995-998.
    [47] Cameroni E, Bowen JE, Rosen LE, et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature, 2022, 602(7898):664-670.
    [4 hamsters from SARS-CoV-2 infection. Nat Commun, 2021, 12(1):4635.
    [71] Hultberg A, Temperton NJ, Rosseels V, et al. Llama- derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules. PLoS One, 2011, 6(4):e17665.
    [72] Xiang YF, Nambulli S, Xiao ZY, et al. Versatile and multivalent nanobodies efficiently neutralize SARS- CoV-2. Science, 2020, 370(6523):1479-1484.
    [73] Xu JL, Xu K, Jung S, et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature, 2021, 595(7866):278-282.
    [74] Ma H, Zeng WH, Meng XZ, et al. Potent neutralization of SARS-CoV-2 by hetero-bivalent alpaca nanobodies targeting the spike receptor-binding domain. J Virol, 2021, 95(10):e02438-20.
    [75] Ma H, Zhang XH, Zheng PY, et al. Hetero-bivalent nanobodies provide broad-spectrum protection against SARS-CoV-2 variants of concern including Omicron. Cell Res, 2022, DOI:10.1038/s41422-022-00700-3.
    [76] Gauhar A, Privezentzev CV, Demydchuk M, et al. Single domain shark VNAR antibodies neutralize SARS-CoV-2 infection in vitro. FASEB J, 2021, 35(11):e21970.
    [77] Ubah OC, Lake EW, Gunaratne GS, et al. Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography. Nat Commun, 2021, 12(1):7325.rough ACE2 receptor mimicry. Nat Commun, 2021, 12(1):250.
    [56] Liu LH, Iketani S, Guo YC, et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature, 2022, 602(7898):676-681.
    [57] 单思思, 王若珂, 张绮, 等. 安巴韦单抗注射液(BRII-196)及罗米司韦单抗注射液(BRII-198) ——中国首个自主知识产权新冠病毒中和抗体联合治疗药物. 中国医药导刊, 2022, 24(1):2-8. Shan SS, Wang RK, Zhang Q, et al. China's first approved novel neutralizing antibody combination therapy against SARS-CoV-2——BRII-196/BRII-198. Chin J Med Guide, 2022, 24(1):2-8(in Chinese).
    [58] Zou J, Li L, Zheng PY, et al. Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance. J Clin Invest, 2022, 132(4):e154987.
    [59] Deng YQ, Zhang NN, Zhang YF, et al. Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters. Cell Res, 2022, 32(4):375-382.
    [60] Lu J, Yin QL, Pei RJ, et al. Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and Omicron variants. Virol Sin, 2022, 37(2):238-247.
    [61] Zhang XH, Luo FY, Zhang HJ, et al. A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2. bioRxiv, 2022, DOI:10.1101/2022.04.26.489529.
    [62] Liu WS, Song HP, Chen Q, et al. Recent advances in the selection and identification of antigen-specific nanobodies. Mol Immunol, 2018, 96:37-47.
    [63] Huo JD, Le Bas A, Ruza RR, et al. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2. Nat Struct Mol Biol, 2020, 27(9):846-854.
    [64] Lu QZ, Zhang ZL, Li HX, et al. Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike protein. J Nanobiotechnology, 2021, 19(1):33.
    [65] Schoof M, Faust B, Saunders RA, et al. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive spike. Science, 2020, 370(6523):1473-1479.
    [66] Dong JB, Huang B, Wang B, et al. Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2. Sci Rep, 2020, 10(1):17806.
    [67] Dong JB, Huang B, Jia ZJ, et al. Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity. Emerg Microbes Infect, 2020, 9(1):1034-1036.
    [68] Hanke L, Vidakovics Perez L, Sheward DJ, et al. An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. Nat Commun, 2020, 11(1):4420.
    [69] Koenig PA, Das H, Liu HJ, et al. Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Science, 2021, 371(6530):eabe6230.
    [70] Li TT, Cai HM, Yao, HB, et al. A synthetic nanobody targeting RBD protects
    引证文献
引用本文

陈玉磊,林锦锦,郑培义,曹敏杰,金腾川. 新冠病毒中和单克隆抗体及纳米抗体研究进展[J]. 生物工程学报, 2022, 38(9): 3173-3193

复制
相关视频

分享
文章指标
  • 点击次数:589
  • 下载次数: 1440
  • HTML阅读次数: 1525
  • 引用次数: 0
历史
  • 收稿日期:2022-04-21
  • 录用日期:2022-06-02
  • 在线发布日期: 2022-09-24
  • 出版日期: 2022-09-25
文章二维码
您是第位访问者
生物工程学报 ® 2025 版权所有

通信地址：中国科学院微生物研究所    邮编：100101

电话：010-64807509   E-mail：cjb@im.ac.cn

技术支持：北京勤云科技发展有限公司