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.