Research Open Access
Like 0



A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002–2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.


The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed.


The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein.


An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2-infected cells and is suitable for use in a sandwich ELISA format.


The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.


Article metrics loading...

Loading full text...

Full text loading...



  1. Drosten C, Günther S, Preiser W, van der Werf S, Brodt HR, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1967-76.  https://doi.org/10.1056/NEJMoa030747  PMID: 12690091 
  2. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al. , SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953-66.  https://doi.org/10.1056/NEJMoa030781  PMID: 12690092 
  3. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.  https://doi.org/10.1038/s41586-020-2012-7  PMID: 32015507 
  4. 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(1):275-7.  https://doi.org/10.1080/22221751.2020.1723441  PMID: 32005086 
  5. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.  https://doi.org/10.1056/NEJMoa2001316  PMID: 31995857 
  6. Coronavirus disease (COVID-19) outbreak Geneva: World Health Organization; 2020. [Accessed 3 May 2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
  7. Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016;3(1):237-61.  https://doi.org/10.1146/annurev-virology-110615-042301  PMID: 27578435 
  8. Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, 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):221-36.  https://doi.org/10.1080/22221751.2020.1719902  PMID: 31987001 
  9. 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(10224):565-74.  https://doi.org/10.1016/S0140-6736(20)30251-8  PMID: 32007145 
  10. Ceraolo C, Giorgi FM. Genomic variance of the 2019-nCoV coronavirus. J Med Virol. 2020;92(5):522-8.  https://doi.org/10.1002/jmv.25700  PMID: 32027036 
  11. Lau SK, Woo PC, Li KS, Huang Y, Tsoi HW, Wong BH, et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci USA. 2005;102(39):14040-5.  https://doi.org/10.1073/pnas.0506735102  PMID: 16169905 
  12. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535-8.  https://doi.org/10.1038/nature12711  PMID: 24172901 
  13. Hu B, Zeng LP, Yang XL, Ge XY, Zhang W, Li B, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 2017;13(11):e1006698.  https://doi.org/10.1371/journal.ppat.1006698  PMID: 29190287 
  14. Yang XL, Hu B, Wang B, Wang MN, Zhang Q, Zhang W, et al. Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus. J Virol. 2015;90(6):3253-6.  https://doi.org/10.1128/JVI.02582-15  PMID: 26719272 
  15. Graham RL, Baric RS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol. 2010;84(7):3134-46.  https://doi.org/10.1128/JVI.01394-09  PMID: 19906932 
  16. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-4.  https://doi.org/10.1038/nature02145  PMID: 14647384 
  17. 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 coronavirus. J Virol. 2020;94(7):e00127-20.  https://doi.org/10.1128/JVI.00127-20  PMID: 31996437 
  18. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562-9.  https://doi.org/10.1038/s41564-020-0688-y  PMID: 32094589 
  19. Keng CT, Zhang A, Shen S, Lip KM, Fielding BC, Tan TH, et al. Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: implications for the development of vaccines and antiviral agents. J Virol. 2005;79(6):3289-96.  https://doi.org/10.1128/JVI.79.6.3289-3296.2005  PMID: 15731223 
  20. Lip KM, Shen S, Yang X, Keng CT, Zhang A, Oh HL, et al. Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J Virol. 2006;80(2):941-50.  https://doi.org/10.1128/JVI.80.2.941-950.2006  PMID: 16378996 
  21. Ng OW, Keng CT, Leung CS, Peiris JS, Poon LL, Tan YJ. Substitution at aspartic acid 1128 in the SARS coronavirus spike glycoprotein mediates escape from a S2 domain-targeting neutralizing monoclonal antibody. PLoS One. 2014;9(7):e102415.  https://doi.org/10.1371/journal.pone.0102415  PMID: 25019613 
  22. 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(7):e237.  https://doi.org/10.1371/journal.pmed.0030237  PMID: 16796401 
  23. Zheng Z, Teo SHC, Arularasu SC, Liu Z, Mohd-Ismail NK, Mok CK, et al. Contribution of Fc-dependent cell-mediated activity of a vestigial esterase-targeting antibody against H5N6 virus infection. Emerg Microbes Infect. 2020;9(1):95-110.  https://doi.org/10.1080/22221751.2019.1708215  PMID: 31906790 
  24. Nakamura T, Yamada KD, Tomii K, Katoh K. Parallelization of MAFFT for large-scale multiple sequence alignments. Bioinformatics. 2018;34(14):2490-2.  https://doi.org/10.1093/bioinformatics/bty121  PMID: 29506019 
  25. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ. Jalview Version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics. 2009;25(9):1189-91.  https://doi.org/10.1093/bioinformatics/btp033  PMID: 19151095 
  26. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol. 2018;35(6):1547-9.  https://doi.org/10.1093/molbev/msy096  PMID: 29722887 
  27. Elbe S, Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Glob Chall. 2017;1(1):33-46.  https://doi.org/10.1002/gch2.1018  PMID: 31565258 
  28. 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(1):382-5.  https://doi.org/10.1080/22221751.2020.1729069  PMID: 32065055 
  29. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-3.  https://doi.org/10.1126/science.abb2507  PMID: 32075877 
  30. Poh WP, Narasaraju T, Pereira NA, Zhong F, Phoon MC, Macary PA, et al. Characterization of cytotoxic T-lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD-integrin-binding motif. J Med Virol. 2009;81(7):1131-9.  https://doi.org/10.1002/jmv.21571  PMID: 19475608 
  31. Miyoshi-Akiyama T, Ishida I, Fukushi M, Yamaguchi K, Matsuoka Y, Ishihara T, et al. Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model. J Infect Dis. 2011;203(11):1574-81.  https://doi.org/10.1093/infdis/jir084  PMID: 21592986 
  32. Zhong X, Yang H, Guo ZF, Sin WY, Chen W, Xu J, et al. B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein. J Virol. 2005;79(6):3401-8.  https://doi.org/10.1128/JVI.79.6.3401-3408.2005  PMID: 15731234 
  33. 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(1):186-93.  https://doi.org/10.1016/j.bbrc.2005.05.089  PMID: 15939399 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error