Structural Analysis of Spike Proteins from SARS-CoV-2 Variants of Concern Highlighting Their Functional Alterations

Abstract

Aim: Mutations in the SARS-CoV-2 spike (S) protein have dramatically changed the transmissibility and pathogenicity of the virus. Therefore, we studied the binding affinity of Omicron spike-receptor binding domain (S-RBD) with human ACE2 receptor. Materials & methods: We used pyDockWEB and HADDOCK 2.4 docking for our study. Results: Computational docking indicated higher binding affinity of Omicron S-RBD as compared with wild-type SARS-CoV-2 and Delta S-RBD with ACE2. Interface analysis suggested four mutated residues of Omicron S-RBD for its enhanced binding. We also showed decreased binding affinity of Omicron and Delta S-RBDs with monoclonal antibodies. Conclusion: Compared with wild-type SARS-CoV-2, Omicron S-RBD exhibit higher binding with ACE2 and lower affinity against monoclonal antibodies.

A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics

“…Among 15 mutations in RBD of Omicron-S, 13 of them are predicted to affect the antibody neutralization through either altering the S-protein conformation or changing its surface charge distribution. Besides 4 mutations (E484A, K417N, N501Y, T478K) 2 , other 9 mutations (G339D, G446S, N440K, Q493R, Q498R, S371L, S373P, S375F, Y505H) are peculiar to Omicron 1 , 44 , 45 . In fact, Omicron has exerted potent capability for immune evasion in the presence of most therapeutic SARS-CoV-2 mAbs 4 – 8 , showing that the affinity of Omicron-S for previous SARS-CoV-2 mAb has become weaker.…”

Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern

“…The SARS-CoV-2 genome comprises 29,903 bp. The Spike protein is a predominant surface antigen of SARS-CoV-2 involved in the docking and penetration of the virus into the target host cells (20)(21)(22). As such, the Spike protein is the main target of the first-generation COVID-19 subunit vaccines aiming mainly at inducing neutralizing antibodies (23,24).…”

Cross-Protection Induced by Highly Conserved Human B, CD4+,and CD8+T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

“…The Spike protein is a surface predominant antigen of SARS-CoV-2 that is involved in the docking and penetration of the virus into the target host cells (20)(21)(22). As such, the Spike protein is the main target of the first-generation COVID-19 subunit vaccines aiming mainly at inducing neutralizing antibodies (23,24).…”

“…Nearly 56% of the 10 billion doses of first-generation COVID-19 vaccines are based on the Spike antigen alone (25), while the remaining 44% of the COVID-19 vaccines were based on whole virion inactivated (WVI) vaccines (26,27). Both the Spike-based COVID-19 sub-unit vaccines and the whole virion-inactivated vaccines were successful (20)(21)(22). However, because the Spike protein is the most mutated SARS-CoV-2 antigen, these first-generation vaccines lead to immune evasion by many new variants and subvariants, such as Omicron XBB1.5 sub-variant (25), (28,29).…”