Impact of the N501Y substitution of SARS-CoV-2 Spike on neutralizing monoclonal antibodies targeting diverse epitopes

Lin Cheng,Bing Zhou,Zheng Zhang,Xiangyang Ge,Bin Ju,Jiazhen Yu,Mingxia Zhang,Shuo Song

doi:10.1186/s12985-021-01554-8

Abstract

The emergence and rapid spread of the B.1.1.7 lineage (VOC-202012/01) SARS-CoV-2 variant has aroused global concern. The N501Y substitution is the only mutation in the interface between the RBD of B.1.1.7 and ACE2, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we assessed the neutralizing activity and binding affinity of a panel of 12 monoclonal antibodies against the wild type and N501Y mutant SARS-CoV-2 pseudovirus and RBD protein, respectively. We found that the neutralization activity and binding affinity of most detected antibodies (10 out of 12) were unaffected, although the N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23. These findings could be of value in the development of therapeutic antibodies.

Highlights

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has emerged in late 2019 and lasted more than a year all over the world
A large number of receptor binding domain (RBD)-specific Neutralizing antibody (nAb) have been identified from convalescent individuals and immunized animals, some of which are promising candidates for
There are seven substitutions (N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H) and three deletions (H69Del, V70Del, and Y144Del) in the spike of the N501Y.V1 variant comparing with the Wuhan-Hu-1 strain, with N501Y the only mutation in the angiotensin-converting enzyme 2 (ACE2) interface of the receptor binding domain (RBD)

Summary

Introduction

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has emerged in late 2019 and lasted more than a year all over the world. It is crucial to test and monitor the neutralizing sensibilities of emerging SARS-CoV-2 variants to the published nAbs especially which are undergoing clinical trials and good candidates for treating and preventing COVID-19. Some researchers have focused on the analysis of viral variants escaping the neutralization of monoclonal nAbs isolated by themselves or published by others and polyclonal nAbs of sera samples from convalescent patients or vaccinated individuals [8,9,10]. We further combined a RBD-specific monoclonal nAbs panel involving twelve published antibodies from different classes with diverse neutralizing epitopes, and measured their neutralizations and binding affinities against the wild type and N501Y mutant SARSCoV-2, which will enrich the research in the field of viral escape and be crucial to the control of COVID-19

Materials and methods

Main text

Findings

Conclusion