Omicron-included mutation-induced changes in epitopes of SARS-CoV-2 spike protein and effectiveness assessments of current antibodies

Molecular Biomedicine

Jianping Hu¹  Huaichuan Duan¹  Yueteng Wang¹  Hubing Shi²  Du Guo²  Yan Cheng² 

[1] Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University;Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center;

关键词: SARS-CoV-2;    Spike protein;    Epitopes;    Antibody;    Drug resistance;   

DOI  :  10.1186/s43556-022-00074-3

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown