An anti-Spike protein N-terminal domain (SARS-CoV-2) antibody.

Phase of research

Potential treatment - pre-clinical evidence

How it helps


Drug status


Supporting references
Contradictory references
AI-suggested references
Clinical trials

General information

COV2-2489 is a SARS-CoV-2-neutralizing antibody recognizing the N-terminal domain (NTD) of Spike protein. It was selected in a screen of convalescent patients’ B cells for SARS-CoV-2-reactive antibodies with neutralizing activity without RBD-binding affinity. The antibody’s neutralizing activity stems from the inhibition of a post-attachment step of the viral infection process. The Fc-effector functions of the antibody provided optimal efficacy in a mouse model (Suryadevara et al., 2021).


Supporting references

Link Tested on Impact factor Notes Publication date
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein
Spike protein Biophysical assay Animal model In vitro Mechanism Antibody
in vitro binding assay; in vitro biophysical assay; Vero cells; Vero E6 cells; MA104 cells; HEK293T cells expressing ACE2; EM; K18-hACE2-transgenic mice; (VSV) SARS-CoV-2 Spike pseudotyped virus; SARS-CoV-2 strain 2019n-CoV/USA_WA1/2020 38.64

The antibody neutralized SARS-CoV-2 live virus and Spike pseudotyped virus with IC50s of 199 ng/mL and 56 ng/mL, respectively. It bound to the Spike N-terminal domain and did not inhibit the interaction between Spike protein RBD and host ACE2. The antibody was shown to bind Spike protein after the viral attachment. Its binding affinity for Spike of the B.1.351 strain was markedly decreased; affinity for the B.1.1.7 version was only slightly smaller. The antibody’s neutralization capacity in MA104 cells and HEK293T cells expressing ACE2 was weaker compared to Vero cells. TMPRSS2 expression did not have an impact. It required intact IgG or F(ab′)2 for neutralizing activity. Both prophylactic and therapeutic administration of the antibody protected model mice in a viral challenge from weight loss, significantly decreased the viral load, and reduced lung inflammation.