Abstract
SARS-CoV-2, the causative virus for COVID-19 has now super-mutated into the Omicron (Om) variant. On its spike (S) glycoprotein alone, more than 30 substitutions have been characterized with 15 within the receptor binding domain (RBD); It therefore calls to question the transmissibility and antibody escapability of Omicron. This study was setup to investigate the Omicron RBD’s interaction with ACE2 (host receptor) and a SARS-CoV-2 neutralizing monoclonal antibody (mAb). In-silico mutagenesis was used to generate the Om-RBD in complex with ACE2 or mAb from the wildtype. HDOCK server was used to redock and score the mAbs in Om-RBD bound state relative to the wildtype. Stability of interaction between all complexes were investigated using all-atom molecular dynamics (MD). Analyses of trajectories showed that Om-RBD has evolved into an efficient ACE2 binder, via pi-pi (Om-RBD-Y501/ACE2-Y41) and salt-bridge (Om-RBD-K493/ACE2-Y41) interactions. Conversely, in binding mAb, it has become less efficient (Center of mass distance of RBD from mAb complex, wildtype ≈ 30 Å, Omicron ≈ 41 Å). Disruption of Om-RBD/mAb complex resulted from loose interaction between Om-RBD and the light chain complementarity-determining region residues. Omicron is expected to be better transmissible and less efficiently interacting with neutralizing convalescent mAbs with consequences on transmissibility provided other mutations within the S protein similarly promote cell fusion and viral entry.
Keywords: COVID-19; Monoclonal antibody (mAbs); Omicron variant; Receptor binding domain (RBD); Spike glycoprotein.
【저자키워드】 COVID-19, Omicron variant, receptor binding domain (RBD), spike glycoprotein., Monoclonal antibody (mAbs), 【초록키워드】 SARS-CoV-2, ACE2, Mutation, S protein, spike, antibody, monoclonal antibody, variant, spike glycoprotein, molecular dynamics, omicron, virus, viral entry, Receptor binding domain, Viral, Transmissibility, RBD, Cell fusion, trajectory, Omicron variant, Neutralizing, glycoprotein, molecular, convalescent, interactions, mAbs, binding, mAb, Mutagenesis, Interaction, Disruption, light chain, Trajectories, setup, host receptor, complex, center, Substitution, wildtype, residues, binding domain, Cell, consequence, complementarity-determining region, was used, investigated, generate, provided, characterized, less, question, promote, complexes, the S protein, expected, 【제목키워드】 SARS-CoV-2, ACE2, convalescent, exhibit,