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TitleThree epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants.
Journal, issue, pagesCell Discov, Vol. 7, Issue 1, Page 53, Year 2021
Publish dateJul 20, 2021
AuthorsJianhui Nie / Jingshu Xie / Shuo Liu / Jiajing Wu / Chuan Liu / Jianhui Li / Yacui Liu / Meiyu Wang / Huizhen Zhao / Yabo Zhang / Jiawei Yao / Lei Chen / Yuelei Shen / Yi Yang / Hong-Wei Wang / Youchun Wang / Weijin Huang /
PubMed AbstractCoronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. ...Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.
External linksCell Discov / PubMed:34285195 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 4.2 Å
Structure data

EMDB-30976:
SARS-CoV-2 spike in complex with the Ab4 neutralizing antibody (State 1)
Method: EM (single particle) / Resolution: 3.4 Å

30977

7e39

EMDB-30977, PDB-7e39:
SARS-CoV-2 spike in complex with the Ab4 neutralizing antibody (State 3)
Method: EM (single particle) / Resolution: 3.7 Å

30978

7e3b

EMDB-30978, PDB-7e3b:
SARS-Cov-2 spike in complex with the Ab5 neutralizing antibody (focused refinement on Fab-RBD)
Method: EM (single particle) / Resolution: 4.2 Å

30979

7e3c

EMDB-30979, PDB-7e3c:
SARS-CoV-2 spike in complex with the Ab1 neutralizing antibody (focused refinement on Fab-RBD)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-30980:
SARS-CoV-2 spike in complex with the Ab5 neutralizing antibody Fab (consensus map)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-30981:
SARS-CoV-2 spike in complex with the Ab1 neutralizing antibody (consensus map)
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Spike / SARS-CoV-2 / Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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