Recent #SARSCoV2 variants in South Africa (B.1.351) and Brazil (P.1) reduce neutralization of patient and vaccinated sera. Our new study reveals the molecular basis of how major classes of antibodies are extremely sensitive to the key mutations. (1/6) biorxiv.org/content/10.110…
We analyzed 1,593 SARS-CoV-2 antibodies targeting the receptor binding domain (RBD), and found that IGHV3-53/3-66 and IGHV1-2 are the two most frequently elicited antibody families. Strikingly, neutralization of all tested antibodies from these germlines was abolished. (2/6)
Most IGHV3-53/3-66 antibodies are structurally convergent to two binding modes, where K417N or E484K abrogates the binding and neutralization. (3/6)
Likewise, IGHV1-2 antibodies are also structurally convergent to two binding modes, where E484K abrogates the binding and neutralization. (4/6)
In contrast, neutralizing antibodies to the cross-reactive CR3022 and S309 sites are largely unaffected. (5/6)