HUMAN IGG1 ANTI-SARS-COV-2 SPIKE NTD ANTIBODY, CHIMERIC MAB (AM121)

Human IgG1 anti-SARS-CoV-2 spike NTD neutralizing antibody is a chimeric mAb combining the constant domains of the human IgG1 molecule with mouse variable regions. This antibody recognizes the SARS-CoV-2 N-terminal domain (NTD).

PRODUCT DETAILS – HUMAN IGG1 ANTI-SARS-COV-2 SPIKE NTD ANTIBODY, CHIMERIC MAB (AM121)

• Antibody binds SARS-CoV-2 NTD
• Isotype – human IgG1, Kappa.
• Presented in PBS
• Greater than 95% purity as determined by SDS-PAGE.
• Suitable for use in ELISA.
• Cross-reactivity with other coronaviruses has not been tested.

BACKGROUND

Human coronaviruses are the major cause of upper respiratory tract illness. They are positive-stranded RNA viruses, and contain the largest viral RNA genomes known to date (27-31 kb). SARS (severe acute respiratory syndrome) and COVID-19 are both caused by human coronaviruses, SARS-CoV and SARS-CoV-2, respectively. The coronavirus spike (S) glycoprotein is a class I viral fusion protein on the outer envelope of the virion that plays a critical role in viral infection by recognizing host cell receptors and mediating fusion of the viral and cellular membranes (Li, 2016). Each monomer of trimeric S protein is about 180 kDa, and contains two subunits, S1 and S2, mediating attachment and membrane fusion, respectively. Two major domains in coronavirus S1 have been identified, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD). Either or both of these S1 domains can function as a receptor-binding domain (RBD), depending on virus; SARS-CoV and MERS-CoV both use C-domain to bind their receptors (Ou et al., 2020). Angiotensin-converting enzyme 2 (hACE2)21 and human dipeptidyl peptidase 4 (hDPP4)22 have been identified as the receptors for SARS-CoV and MERS-CoV, respectively. While S proteins of SARS-CoV-2 share about 76% amino acid identities with SARS-CoV, the amino acid sequence of potential RBD of SARS-CoV-2 is only about 74% homologous to that of SARS-CoV. It has been reported that human ACE2 is also the entry receptor of SARS-CoV-2, and that a serine protease is important for SARS-CoV-2 Spike activation (Hoffmann et al., 2020).The RBD is responsible for binding to ACE2, whereas the function of NTD is not well understood. In some coronaviruses, the NTD may recognize specific sugar moieties upon initial attachment and might play an important role in the prefusion-to-postfusion transition of the S protein. For example, the NTD of the MERS-CoV S protein can serve as a critical epitope for neutralizing antibodies (Zhou et al., 2019) and Chi et al. identified an antibody that potently neutralizes SARS-CoV-2 by binding to the NTD. These results strongly suggest that the NTD is a promising target for therapeutic mAbs against COVID-19 (Chi et al., 2020).

REFERENCES

• Chi X, Yan R, Zhang J, Zhang G, Zhang Y, Hao M, Zhang Z, Fan P, Dong Y, Yang Y, Chen Z, Guo Y, Zhang J, Li Y, Song X, Chen Y, Xia L, Fu L, Hou L, Xu J, Yu C, Li J, Zhou Q, Chen W. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020 Aug 7;369(6504):650-655.
• Hoffmann M, Kleine-Weber H, Schroeder S, et al. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;S0092-8674(20)30229-4.
  Li F. (2016). Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016;3(1):237–261.
• Ou X, Liu Y, Lei X, et al. (2020). Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.
• Zhou H, Chen Y, Zhang S, Niu P, Qin K, Jia W, Huang B, Zhang S, Lan J, Zhang L, Tan W, Wang X. Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein. Nat Commun. 2019 Jul 11;10(1):3068.