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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.

Research topics

  • SARS-CoV-2 and COVID-19 Research
  • COVID-19 Clinical Research Studies
  • Complement system in diseases

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DOI: 10.22541/au.170667100.04888721/v1

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