biostudies-literatureRosen LENational Institute of Allergy and Infectious DiseasesPEW Charitable TrustsSearle Scholars ProgramHoward Hughes Medical InstituteNIAID NIH HHSBurroughs Wellcome FundVir Biotechnology IncNCI NIH HHSDamon Runyon Cancer Research FoundationNIGMS NIH HHS7196-7213.e26https://www.ebi.ac.uk/biostudies/studies/S-EPMC11645210biostudies-literatureUnknown187(25)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinitCellA potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.PMC11645210P30 CA042014DP1 AI158186P30 CA008748P30 GM133894F31 AI174573P30 GM124169P01 AI16796675N93022C00036Bohan DRajesh AZhang IGuarino BTsu Bdi Iulio JStarr TNSchnell GCzudnochowski NPark YJCorti DRietz TSprouse KRAddetia ATaylor ALBenigni FSubramanian SErrico JMDaCosta YTortorici MASchmid MAPizzuto MSNoack JRosen LEAcosta RWhelan SPJDe Marco AHauser KDang HVTelenti AChartron JWPinto DLanzavecchia ABourhy HDellota ECameroni ELee JKergoat LForeman WBde Melo GDLiu ZCusumano GPurcell LAVeesler DLempp FASnell GZatta FSaliba CBrown JMiller JLGiurdanella MZepeda SKTao QfalseA potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinit2024-01-01T00:00:00Z2024 Dec2026-06-03T03:08:27.281Z2025-04-04T01:54:34.999ZS-EPMC116452103938386310.1016/j.cell.2024.09.026