Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor

• Published in: Biochemical and biophysical research communications Vol. 590; pp. 34 - 41
• Main Authors: Lupala, Cecylia S., Ye, Yongjin, Chen, Hong, Su, Xiao-Dong, Liu, Haiguang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.01.2022
• Subjects: ACE2; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - metabolism; Binding Sites; COVID-19 - metabolism; COVID-19 infection; Host-Pathogen Interactions; Humans; hydrogen; Molecular Docking Simulation; molecular dynamics; Molecular Dynamics Simulation; Mutation; neutralization; Omicron mutant; pandemic; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Receptor binding domain; SARS-CoV-2; SARS-CoV-2 - chemistry; SARS-CoV-2 - genetics; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; solvents; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; surface area; viruses; ACE2; SARS-CoV-2; Omicron mutant; Molecular dynamics simulation; Receptor binding domain
• DOI: 10.1016/j.bbrc.2021.12.079
• ISSN: 0006-291X; 1090-2104

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to more than 270 million infections and 5.3 million of deaths worldwide. Several major variants of SARS-CoV-2 have emerged and posed challenges in controlling the pandemic. The recently occurred Omicron variant raised serious concerns about reducing the efficacy of vaccines and neutralization antibodies due to its vast mutations. We have modelled the complex structure of the human ACE2 protein and the receptor binding domain (RBD) of Omicron Spike protein (S-protein), and conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron RBD binds more strongly to the human ACE2 protein than the original strain. The mutations at the ACE2-RBD interface enhance the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area. •Structure prediction and refinement of SARS-CoV-2 spike protein RBD-ACE2 complex for Omicron variant.•Molecular dynamics simulations reveal stronger binding interactions between RBD and ACE2 protein in Omicron.•Mutations on Omicron RBD yield more hydrogen bonds, residue contacts and larger buried surface at the ACE2-RBD interface.