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Human neutralizing antibodies to SARS-CoV-2 mutational coldspots that broadly crossreact with Orthocoronavirinae
Swiss Medical Weekly ; 152:11S, 2022.
Article in English | EMBASE | ID: covidwho-2040823
ABSTRACT
Most SARS-CoV-2 neutralizing antibodies described to date target the receptor binding and N-terminal domains (RBD and NTD) of the Spike (S) protein. However, mutations such as those found in SARSCoV- 2 variants of concern (VOC), cause amino acid (aa) changes in the RBD and NTD that diminish or abrogate the effectiveness of vaccines and antiviral monoclonal antibodies that are currently in the clinic. We hypothesized that regions of S may be under selective pressure to maintain their aa sequence unchanged because they are essential for its function. We identified 15 regions with infrequent aa changes and devoid of aa changes in SARS-CoV-2 VOC one coldspot includes the S2' cleavage site and a portion of the fusion peptide (FP), a second one is at the stem helix that precedes the heptad repeat 2 region (HR2). We specifically searched for and identified human antibodies targeting FP and HR2 coldspots in plasma samples from a COVID-19 convalescent cohort. Neutralizing antibodies to the FP are broadly cross-reactive against all human coronaviruses and non-human coronaviruses of the four genera (alpha to delta). Antibody hr2.016, which binds to a conserved epitope near the HR2 helix, neutralizes SARS-CoV-2 variants of concern and is superior to previously described antibodies to this region. Thus, coldspot-guided antibody discovery reveals natural neutralizing antibodies that are broadly cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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Collection: Databases of international organizations Database: EMBASE Language: English Journal: Swiss Medical Weekly Year: 2022 Document Type: Article

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Collection: Databases of international organizations Database: EMBASE Language: English Journal: Swiss Medical Weekly Year: 2022 Document Type: Article