Monoclonal Antibody-Light chain CDR1/Spike Glycoprotein Receptor Binding
Domain Dissociation Explains Antibody Escape Mechanism in
L452R-SARS-CoV-2
Abstract
Most of the well-characterized innate antibodies elicited by exposure to
SARS-CoV-2 or a vaccine targets the spike glycoprotein receptor-binding
domain (RDB) which doubles as the angiotensin-converting enzyme 2 (ACE2,
receptor) binding. RBD mutation is therefore a potential health concern
in COVID-19 pandemic. RBD-L452R-SARS-CoV-2 exhibits increased
transmissibility and immune evasion with an unknown underlying
mechanisms. The immune evasion mechanism was investigated here. in R452,
loss of hydrophobic interaction between RBD-L452/HCDR3-I103 disrupts
RBD-E484/heavy-chain-R112 salt-bridge, and cation-π interaction between
RBD-E484/mAB-Y32(LcCDR1). Unburied RBD flips ~64° from
the antibody plane, losing all interaction with the mAB light chain-CDR;
thus, making ternary complex thermodynamically unstable.