Characteristics of  SARS-CoV-2 neutralizing antibodies targeting NTD Spike protein: Effects of Glycans and Variants

A group from Columbia University, etc. has reported about characteristics of SARS-CoV-2 neutralizing antibodies targeting NTD Spike protein.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953435/

Totally 17 NTD antibodies have been already published. It was found that these antibodies target a specific area (called Supersite) on NTD of the spike protein. The NTD supersite was located at the periphery of the spike protein, distal from the 3-fold axis, and facing away from the viral membrane. This surface was surrounded by four N-glycans, N17, N74, N122, and N149, and nominally “glycan free,” although there are some glycan coverage because of the dynamic motional fluctuation of glycans. And also, the supersite had strong positive electrostatic potential, while recognizing antibodies had complementary strong electronegative potential.

The SARS-CoV-2 variants, particularly B.1.1.7 and B.1.351, are concerning due to increased infectivity, and these variants escape most NTD-directed neutralizing antibodies. B.1.1.7 includes NTD deletion mutations D69-70 and D144, and strain B.1.351 includes NTD mutations D242-244 and R246I. The mutated positions including 144, 242-244, and 246 are all within the NTD supersite. While the deletion at 69-70 is outside of the supersite, it forms part of the hairpin N2 loop of NTD. So, its deletion could significantly impact the conformation of the NTD supersite.