tetano
Editor, Senior Moderator
PLoS Biol
. 2026 Oct 1;24(10):e3003882.
doi: 10.1371/journal.pbio.3003882. eCollection 2026 Oct.
Ayush Upadhyay 1 2 , Jeffrey Seow 1 , Yilmaz Alguel 2 , Joseph Newman 3 , Nazia Thakur 3 , Abigail L Hay 3 , Jerry C H Tam 1 , Andrea Nans 4 , Richard J Orton 5 , Dalan Bailey 3 , Peter Cherepanov 2 6 , Katie J Doores 1
Affiliations Expand
The continuing evolution of SARS-CoV-2 variants of concern, and the increasing spillover potential of sarbecoviruses into the human population presents an important and urgent need to discover cross-reactive monoclonal antibodies (mAbs) for future therapeutic use and identify conserved neutralising epitopes that can be used for rationale design of broadly protective sarbecovirus vaccines. Here we study the neutralising epitopes on WIV-1 Spike of three mAbs that confer broad sarbecovirus and SARS-CoV-2 variant neutralisation, including XEC, JN.1, and XFG. mAb V1WT_06 binds a highly conserved RBD site V epitope that is mediated by the heavy chain alone. V1WT_06 contact residues are highly conserved in circulating viruses suggesting that the epitope is evolutionarily and functionally constrained. mAbs V1WT_41 and VA14_26 bind overlapping RBD class 4 epitopes with differing angles of approach that impact on the degree of ACE2 competition. We show that neutralisation by these mAbs is maintained when virus entry is via Japanese horseshoe bat and Halcyon horseshoe bat ACE2s. These mAbs are ideal candidates for therapeutic antibody development and inform the rational design of pan-betacoronavirus vaccines.
. 2026 Oct 1;24(10):e3003882.
doi: 10.1371/journal.pbio.3003882. eCollection 2026 Oct.
Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses
Ayush Upadhyay 1 2 , Jeffrey Seow 1 , Yilmaz Alguel 2 , Joseph Newman 3 , Nazia Thakur 3 , Abigail L Hay 3 , Jerry C H Tam 1 , Andrea Nans 4 , Richard J Orton 5 , Dalan Bailey 3 , Peter Cherepanov 2 6 , Katie J Doores 1
Affiliations Expand
- PMID: 42821509
- PMCID: PMC13630248
- DOI: 10.1371/journal.pbio.3003882
Abstract
The continuing evolution of SARS-CoV-2 variants of concern, and the increasing spillover potential of sarbecoviruses into the human population presents an important and urgent need to discover cross-reactive monoclonal antibodies (mAbs) for future therapeutic use and identify conserved neutralising epitopes that can be used for rationale design of broadly protective sarbecovirus vaccines. Here we study the neutralising epitopes on WIV-1 Spike of three mAbs that confer broad sarbecovirus and SARS-CoV-2 variant neutralisation, including XEC, JN.1, and XFG. mAb V1WT_06 binds a highly conserved RBD site V epitope that is mediated by the heavy chain alone. V1WT_06 contact residues are highly conserved in circulating viruses suggesting that the epitope is evolutionarily and functionally constrained. mAbs V1WT_41 and VA14_26 bind overlapping RBD class 4 epitopes with differing angles of approach that impact on the degree of ACE2 competition. We show that neutralisation by these mAbs is maintained when virus entry is via Japanese horseshoe bat and Halcyon horseshoe bat ACE2s. These mAbs are ideal candidates for therapeutic antibody development and inform the rational design of pan-betacoronavirus vaccines.