8D47

fp.006 Fab in complex with SARS-CoV-2 Fusion Peptide

Summary for 8D47

• Entry DOI: 10.2210/pdb8d47/pdb
• Descriptor: fp.006 light chain, fp.006 heavy chain, SARS-CoV-2 fusion peptide, ... (7 entities in total)
• Functional Keywords: antibody, fusion peptide, tmprss2 binding site, complex, antiviral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 104087.60

Authors

Abernathy, M.E.,Barnes, C.O. (deposition date: 2022-06-01, release date: 2022-12-21, Last modification date: 2024-10-23)

Primary citation

Bianchini, F.,Crivelli, V.,Abernathy, M.E.,Guerra, C.,Palus, M.,Muri, J.,Marcotte, H.,Piralla, A.,Pedotti, M.,De Gasparo, R.,Simonelli, L.,Matkovic, M.,Toscano, C.,Biggiogero, M.,Calvaruso, V.,Svoboda, P.,Cervantes Rincon, T.,Fava, T.,Podesvova, L.,Shanbhag, A.A.,Celoria, A.,Sgrignani, J.,Stefanik, M.,Honig, V.,Pranclova, V.,Michalcikova, T.,Prochazka, J.,Guerrini, G.,Mehn, D.,Ciabattini, A.,Abolhassani, H.,Jarrossay, D.,Uguccioni, M.,Medaglini, D.,Pan-Hammarstrom, Q.,Calzolai, L.,Fernandez, D.,Baldanti, F.,Franzetti-Pellanda, A.,Garzoni, C.,Sedlacek, R.,Ruzek, D.,Varani, L.,Cavalli, A.,Barnes, C.O.,Robbiani, D.F.
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.
Sci Immunol, 8:eade0958-eade0958, 2023

PubMed Abstract: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.

PubMed: 36701425
DOI: 10.1126/sciimmunol.ade0958

Experimental method

X-RAY DIFFRACTION (2 Å)