Fig 1.
SARS-CoV-2 spike protein structure, conformation, and targets of RBD-dependent mAbs.
(A) SARS-CoV-2 spike protein regions with amino acid position numbering are shown, which includes S1 domain regions: the SP, NTD, RBD, and RBM and S2 domain regions: FP, HR1 and HR2, TM, and CP. The glycosylation sites are numbered and marked with Y-like structures in blue. (B) Different conformations of spike protein (PDB: 7DF3, 6XKL, 7EB5, and 7KML, left to right). (C) Representation of 4 classes of SARS-CoV-2 RBD dependent mAbs. Antibody variable heavy chain region (sky blue) and light chain variable region (magenta) are marked. Antibody constant regions were removed from the bound Fab for clarity. The RBD is shown in (pale green) color and antibody contacts on RBD are marked in red (PDB ID: left to right, 7CM4 (CT-P59), 7CHF (BD-368-2), 7K90 (C144), and 6R6X (S304 (left) and S309 (right)). RBD class IV core II region targeting mAbs are shown in blue. CP, cytoplasmic tail; FP, fusion peptide; HR1, heptad repeat 1; HR2, heptad repeat 2; mAb, monoclonal antibody; NTD, N-terminal domain; PDB, Protein Data Bank; RBD, receptor-binding domain; RBM, receptor-binding motif; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SP, signal peptide; TM, transmembrane domain.
Fig 2.
Neutralization potential of therapeutic mAbs against SARS-CoV-2 VOCs and VOIs.
(A) Neutralization potential of SARS-CoV-2 mAbs at various stages of development/clinic against VOCs and VOIs. Here, fold change represents the reduction in IC50 values of SARS-CoV-2 variant neutralization in comparison to wild-types virus. The abbreviations for mAbs in the clinic (EUA) are the following: Bam, Bamlanivimab (LY-CoV555); Ete, Etesevimab (LY-CoV016 or JS016 or CB6); Bam/Ete, Bamlanivimab+Etesevimab; Cas, Casirivimab (REGN10933); Imd, Imdevimab (REGN10987); Cas/Imd, Casirivimab+imdevimab (REGN-COV2); Cil, Cilgavimab (COV2-2130 or AZD1061); Tix, Tixagevimab (COV2-2196 or AZD8895); Tix/Cil, Tixagevimab+Cilgavimab; Sot, Sotrovimab (Vir-7831 or S309); Reg, Regdanvimab (CT-P59). (B) List of mutations present in the current SARS-CoV-2 VOCs and VOIs. EUA, emergency use authorization; mAb, monoclonal antibody; RBD, receptor-binding domain; S2, S2 subunit; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SD1, subdomain 1; SD2, subdomain 2; SP, signal peptide; VOC, variant of concern; VOI, variant of interest.