Omicron-included mutation-induced changes in epitopes of SARS-CoV-2 spike protein and effectiveness assessments of current antibodies
Open Access
- 24 April 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Biomedicine
- Vol. 3 (1), 1-18
- https://doi.org/10.1186/s43556-022-00074-3
Abstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading globally and continues to rage, posing a serious threat to human health and life quality. Antibody therapy and vaccines both have shown great efficacy in the prevention and treatment of COVID-19, whose development progress and adaptation range have attracted wide attention. However, with the emergence of variant strains of SARS-CoV-2, the neutralization activity of therapeutic or vaccine-induced antibodies may be reduced, requiring long-term virus monitoring and drug upgrade in response to its evolution. In this paper, conformational changes including continuous epitopes (CPs), discontinuous epitopes (DPs) and recognition interfaces of the three representative SARS-CoV-2 spike protein (SP) mutants (i.e., the Delta (B.1.617.2), Mu (B.1.621) and Omicron (B.1.1.529) strains), were analyzed to evaluate the effectiveness of current mainstream antibodies. The results showed that the conformation of SP wild type (WT) and mutants both remained stable, while the local antigenic epitopes underwent significant changes. Sufficient flexibility of SP CPs is critical for effective antibody recognition. The DPs of Delta, Mu and Omicron variants have showed stronger binding to human angiotensin converting enzyme-2 (hACE2) than WT; the possible drug resistance mechanisms of antibodies against three different epitopes (i.e., NTD_DP, RBD1_DP and RBD2_DP) were also proposed, respectively; the RBD2 of Delta, NTD of Mu, NTD and RBD2 of Omicron are deserve more attention in the subsequent design of next-generation vaccines. The simulation results not only revealed structural characteristics of SP antigenic epitopes, but also provided guidance for antibody modification, vaccine design and effectiveness evaluation.Keywords
Funding Information
- State Administration of Traditional Chinese Medicine of the People's Republic of China (2018KF006)
- Sichuan Science and Technology Program (2019YFH0054)
This publication has 110 references indexed in Scilit:
- PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa PredictionsJournal of Chemical Theory and Computation, 2011
- Prediction of antigenic epitopes on protein surfaces by consensus scoringBMC Bioinformatics, 2009
- Toward Automatic Reconstruction of a Highly Resolved Tree of LifeScience, 2006
- MMTSB Tool Set: enhanced sampling and multiscale modeling methods for applications in structural biologyJournal of Molecular Graphics and Modelling, 2004
- Development and testing of a general amber force fieldJournal of Computational Chemistry, 2004
- ChemInform Abstract: Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum ModelsChemInform, 2001
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996
- The double cubic lattice method: Efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assembliesJournal of Computational Chemistry, 1995
- Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water modelsJournal of Computational Chemistry, 1992
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983