Characteristics of 12 monoclonal antibodies targeting to SARS-CoV-2 NTD 

A group from Israel Institute for Biological Research, etc. has reported on characteristics of 12 mAbs targeting to SARS-CoV-2 NTD.
https://pubmed.ncbi.nlm.nih.gov/33937725/

12 antibodies (from BLN1 to BLN14) targeting to SARS-CoV-2 NTD were able to efficiently neutralize SARS-CoV-2, exhibiting IC50 values ranging from 54.9 µg/ml for BLN8, to a highly potent values of 0.008 µg/ml for mAbs BLN1 and BLN12. All mAb specificity to NTD was confirmed with ELISA against NTD, and also in detail by an peptide array derived from the entire S1 protein. Then, the effects of glycan modification onto mAbs were investigate by using a glycan array and also with a competition assay adding glycans as inhibitors. While there was very low binding to most examined glycans, mAbs revealed a strong preference to LacNAc and its sialo-form suggesting that the interactions with the N-glycans are involved in the binding to NTD of BLN4 and BLN12 in particular.

It was recently reported that in addition to the “canonical” ACE2 receptor binding by RBD, SARS-CoV-2 NTD interacts with C-type lectin receptors, including L-SIGN and DC-SIGN as an alternative route for SARS-CoV-2 infection and entry into host cells. So, the ability of four representative mAbs to inhibit the interaction of the NTD with L-SIGN, was examined. In the presence of selected anti-NTD mAbs, inhibition efficiency ranged from approximately 25% binding inhibition by BLN14 to 50% inhibition by BLN4. It should be noted, that the observed binding inhibition may be the result of steric interference of L-SIGN binding to NTD, and not necessarily direct blocking of the NTD glycans, involved in binding to L-SIGN.

If L-SIGN and DC-SIGN are indeed alternative receptors for SARS-CoV-2 and mediate its infection of cells in many tissues lacking hACE2, it may be speculated that anti-NTD mAbs may also exert their therapeutic activity by limiting the spreading of the virus in the body. As a conclusion, BLN12 and BLN14 mAbs would represent excellent candidates for therapy of SARS-CoV-2, possibly in combination with anti-RBD mAbs as a cocktail mAb for SARS-CpoV-2.