8dtt
From Proteopedia
(Difference between revisions)
| Line 13: | Line 13: | ||
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-A resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection. | Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-A resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection. | ||
| - | Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.,Dacon C, Peng L, Lin TH, Tucker C, Lee CD, Cong Y, Wang L, Purser L, Cooper AJR, Williams JK, Pyo CW, Yuan M, Kosik I, Hu Z, Zhao M, Mohan D, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Murphy M, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Doranz BJ, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Mascola JR, Holbrook MR, Nemazee D, Wilson IA, Tan J Cell Host Microbe. | + | Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.,Dacon C, Peng L, Lin TH, Tucker C, Lee CD, Cong Y, Wang L, Purser L, Cooper AJR, Williams JK, Pyo CW, Yuan M, Kosik I, Hu Z, Zhao M, Mohan D, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Murphy M, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Doranz BJ, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Mascola JR, Holbrook MR, Nemazee D, Wilson IA, Tan J Cell Host Microbe. 2023 Jan 11;31(1):97-111.e12. doi: 10.1016/j.chom.2022.10.010. , Epub 2022 Nov 7. PMID:36347257<ref>PMID:36347257</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Crystal structure of SARS-CoV-2 spike stem helix peptide in complex with neutralizing antibody COV93-03
| |||||||||||
