Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2

Guangyu Zhou, Qi Zhao, Guangyu Zhou, Qi Zhao

Abstract

A newly identified novel coronavirus (SARS-CoV-2) is causing pneumonia-associated respiratory syndrome across the world. Epidemiology, genomics, and pathogenesis of the SARS-CoV-2 show high homology with that of SARS-CoV. Current efforts are focusing on development of specific antiviral drugs. Therapeutic neutralizing antibodies (NAbs) against SARS-CoV-2 will be greatly important therapeutic agents for the treatment of coronavirus disease 2019 (COVID-19). Herein, the host immune responses against SARS-CoV discussed in this review provide implications for developing NAbs and understanding clinical interventions against SARS-CoV-2. Further, we describe the benefits, challenges and considerations of NAbs against SARS-CoV-2. Although many challenges exist, NAbs still offer a therapeutic option to control the current pandemic and the possible re-emergence of the virus in the future, and their development therefore remains a high priority.

Keywords: COVID-19; Neutralizing antibody; SARS-CoV-2; severe acute respiratory syndrome.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

© The author(s).

Figures

Figure 1
Figure 1
Schematic representation of the coronavirus and spike protein. (A) The coronavirus structure. The viral surface proteins (spike, envelope and membrane glycoproteins) are embedded in a lipid bilayer envelope. (B) Comparison of the spike (S) proteins of SARS-CoV and SARS-CoV-2. RBD, receptor-binding domain; RBM, receptor-binding motif; HR1/2, heptad repeat 1/2.
Figure 2
Figure 2
Schematic mechanism of the neutralizing antibodies. Competition of the neutralizing antibody with the receptor (ACE2) for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein is shown. The protruding portion (violet) of RBD is both the ACE2 receptor-binding site and the antibody epitope.

References

    1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020. 38, 727-33.
    1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–74.
    1. Jiang S, Xia S, Ying T, Lu L. A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome. Cell Mol Immunol. 2020. doi: 10.1038/s41423-020-0372-4. [Epub ahead of print]
    1. Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing. Radiology. 2020. doi: 10.1148/radiol.2020200343. [Epub ahead of print]
    1. Li G, Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV) Nature Reviews Drug Discovery. 2020. doi: 10.1038/d41573-020-00016-0. [Epub ahead of print]
    1. Klasse PJ. Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives. Adv Biol. 2014;2014:157895.
    1. Coughlin MM, Prabhakar BS. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential. Rev Med Virol. 2012;22:2–17.
    1. Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J. 2019;16:69.
    1. Li F. Evidence for a common evolutionary origin of coronavirus spike protein receptor-binding subunits. J Virol. 2012;86:2856–8.
    1. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, 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. doi: 10.1007/s11427-020-1637-5. [Epub ahead of print]
    1. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. 2020. doi: 10.1128/JVI.00127-20. [Epub ahead of print]
    1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020. doi: 10.1038/s41586-020-2012-7. [Epub ahead of print]
    1. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020. doi: 10.1126/science.abb2507. [Epub ahead of print]
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Liu J, Zheng X, Tong Q, Li W, Wang B, Sutter K, Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020. doi: 10.1002/jmv.25709. [Epub ahead of print]
    1. Li C, Xu X. Host Immune Responses to SARS Coronavirus in Humans. Molecular Biology of the SARS-Coronavirus. Heidelberg: Springer. 2010.
    1. Frieman M, Heise M, Baric R. SARS coronavirus and innate immunity. Virus Res. 2008;133:101–12.
    1. Liu L, Wei Q, Nishiura K, Peng J, Wang H, Midkiff C. et al. Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques. Mucosal Immunol. 2016;9:1089–101.
    1. Tseng CT, Perrone LA, Zhu H, Makino S, Peters CJ. Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. J Immunol. 2005;174:7977–85.
    1. Thiel V, Weber F. Interferon and cytokine responses to SARS-coronavirus infection. Cytokine Growth Factor Rev. 2008;19:121–32.
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020; doi: 10.1001/jama. 2020. 1585. [Epub ahead of print]
    1. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J. et al. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia] Zhonghua Jie He He Hu Xi Za Zhi. 2020;43:e005.
    1. Janice Oh HL, Ken-En Gan S, Bertoletti A, Tan YJ. Understanding the T cell immune response in SARS coronavirus infection. Emerg Microbes Infect. 2012;1:e23.
    1. Panesar NS. Lymphopenia in SARS. Lancet. 2003;361:1985.
    1. Hui DS, E IA, Madani TA, Ntoumi F, Kock R, Dar O. et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264–6.
    1. Li G, Chen X, Xu A. Profile of specific antibodies to the SARS-associated coronavirus. N Engl J Med. 2003;349:508–9.
    1. Cheng M, Chan CW, Cheung RC, Bikkavilli RK, Zhao Q, Au SW. et al. Cross-reactivity of antibody against SARS-coronavirus nucleocapsid protein with IL-11. Biochem Biophys Res Commun. 2005;338:1654–60.
    1. Woo PC, Lau SK, Wong BH, Chan KH, Chu CM, Tsoi HW. et al. Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in patients with pneumonia due to the SARS coronavirus. Clin Diagn Lab Immunol. 2004;11:665–8.
    1. Cao WC, Liu W, Zhang PH, Zhang F, Richardus JH. Disappearance of antibodies to SARS-associated coronavirus after recovery. N Engl J Med. 2007;357:1162–3.
    1. Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR. et al. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 2004;10:871–5.
    1. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H. et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019;4:e123158.
    1. Nie Y, Wang G, Shi X, Zhang H, Qiu Y, He Z. et al. Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection. J Infect Dis. 2004;190:1119–26.
    1. Wang Y, Shan Y, Gao X, Gong R, Zheng J, Zhang XD. et al. Screening and expressing HIV-1 specific antibody fragments in Saccharomyces cerevisiae. Mol Immunol. 2018;103:279–85.
    1. Li D, Liu J, Zhang L, Xu T, Chen J, Wang L. et al. N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies. Virol Sin. 2015;30:449–56.
    1. Zhang MY, Choudhry V, Xiao X, Dimitrov DS. Human monoclonal antibodies to the S glycoprotein and related proteins as potential therapeutics for SARS. Curr Opin Mol Ther. 2005;7:151–6.
    1. Prabakaran P, Zhu Z, Xiao X, Biragyn A, Dimitrov AS, Broder CC. et al. Potent human monoclonal antibodies against SARS CoV, Nipah and Hendra viruses. Expert Opin Biol Ther. 2009;9:355–68.
    1. Zhu Z, Prabakaran P, Chen W, Broder CC, Gong R, Dimitrov DS. Human monoclonal antibodies as candidate therapeutics against emerging viruses and HIV-1. Virol Sin. 2013;28:71–80.
    1. Jin Y, Lei C, Hu D, Dimitrov DS, Ying T. Human monoclonal antibodies as candidate therapeutics against emerging viruses. Front Med. 2017;11:462–70.
    1. Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004;279:3197–201.
    1. Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK. et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. 2004;101:2536–41.
    1. van den Brink EN, Ter Meulen J, Cox F, Jongeneelen MA, Thijsse A, Throsby M. et al. Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J Virol. 2005;79:1635–44.
    1. ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F. et al. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med. 2006;3:e237.
    1. Zhu Z, Chakraborti S, He Y, Roberts A, Sheahan T, Xiao X. et al. Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc Natl Acad Sci U S A. 2007;104:12123–8.
    1. Coughlin M, Lou G, Martinez O, Masterman SK, Olsen OA, Moksa AA. et al. Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse. Virology. 2007;361:93–102.
    1. Greenough TC, Babcock GJ, Roberts A, Hernandez HJ, Thomas WD Jr, Coccia JA. et al. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J Infect Dis. 2005;191:507–14.
    1. Duan J, Yan X, Guo X, Cao W, Han W, Qi C. et al. A human SARS-CoV neutralizing antibody against epitope on S2 protein. Biochem Biophys Res Commun. 2005;333:186–93.
    1. Elshabrawy HA, Coughlin MM, Baker SC, Prabhakar BS. Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing. PLoS One. 2012;7:e50366.
    1. Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000Research. 2020;9:72.
    1. Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH. et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005;24:44–6.
    1. Kraft CS, Hewlett AL, Koepsell S, Winkler AM, Kratochvil CJ, Larson L. et al. The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States. Clin Infect Dis. 2015;61:496–502.
    1. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020;9:275–7.
    1. Tian X, Li C, Huang A, Xia S, Lu S, Shi Z. et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9:382–5.
    1. Group PIW, Multi-National PIIST, Davey RT Jr, Dodd L, Proschan MA, Neaton J. et al. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. N Engl J Med. 2016;375:1448–56.
    1. Zhao Q, Ahmed M, Tassev DV, Hasan A, Kuo TY, Guo HF. et al. Affinity maturation of T-cell receptor-like antibodies for Wilms tumor 1 peptide greatly enhances therapeutic potential. Leukemia. 2015;29:2238–47.
    1. Li D, Gong R, Zheng J, Chen X, Dimitrov DS, Zhao Q. Engineered antibody CH2 domains binding to nucleolin: Isolation, characterization and improvement of aggregation. Biochem Biophys Res Commun. 2017;485:446–53.
    1. Zhao Q, Ahmed M, Guo HF, Cheung IY, Cheung NK. Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8. J Biol Chem. 2015;290:13017–27.
    1. Barderas R, Desmet J, Timmerman P, Meloen R, Casal JI. Affinity maturation of antibodies assisted by in silico modeling. Proc Natl Acad Sci U S A. 2008;105:9029–34.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться