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Review
. 2021 Sep 27:12:752003.
doi: 10.3389/fimmu.2021.752003. eCollection 2021.

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

Lok Bahadur Shrestha  1   2 , Nicodemus Tedla  1 , Rowena A Bull  1   2
Affiliations
Review

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

Lok Bahadur Shrestha et al. Front Immunol. .

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.

Keywords: CDR; SARS-COV-2 variants; broadly neutralising antibodies; delta variant; monoclonal antibody.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Domain architecture of SARS-COV-2 spike protein. (B) Structure of SARS-COV-2 virus and interaction of the receptor binding domain with human angiotensin converting enzyme 2 (hACE-2). (C) Trimeric spike protein showing RDB in closed state (down conformation, left) and open state (up conformation, right). Each color represents a monomer. RBD, receptor binding domain; CTD, C-terminal domain; NTD, N-terminal domain, hACE-2, human angiotensin converting enzyme-2; S1, spike protein 1; S2, spike protein 2; CT, Cytoplasmic tail; TM, transmembrane domain; FCS, Furin cleavage site, the numbers refer to amino acid residues. Figure created using Biorender, Pymol and Microsoft PowerPoint.
Figure 2
Figure 2
Ribbon representation of Fab region of a human antibody. The heavy chains are shown in cyan, while light chains are shown in pink. Complementarity determining regions (CDR) of heavy chain (CDRH1, CDR-H2, CDR-H3) are shown in red, CDR of light chain (CDR-L1, CDR-L2, CDR-L3) are shown in yellow. Figure drawn by using Pymol; residues obtained from PDB (www.rcsb.com) using following PDB ID 7CR5.
Figure 3
Figure 3
The antibody binding epitopes in the RBD of SARS-COV-2 as classified by Barnes et al. Class 1 antibodies are represented as spheres in pink color; class 2 as cyan; class 3 as red and class 4 as yellow. Figure drawn by using Pymol; residues obtained from PDB (www.rcsb.com) using following PDB ID (7K8M, 7K90, 7JX3, 7JN5, 6ZER). *nAb not described in this paper.
See this image and copyright information in PMC

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