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TitleHuman neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.
Journal, issue, pagesSci Immunol, Vol. 8, Issue 81, Page eade0958, Year 2023
Publish dateMar 17, 2023
AuthorsFilippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca Simonelli / Milos Matkovic / Chiara Toscano / Maira Biggiogero / Veronica Calvaruso / Pavel Svoboda / Tomás Cervantes Rincón / Tommaso Fava / Lucie Podešvová / Akanksha A Shanbhag / Andrea Celoria / Jacopo Sgrignani / Michal Stefanik / Vaclav Hönig / Veronika Pranclova / Tereza Michalcikova / Jan Prochazka / Giuditta Guerrini / Dora Mehn / Annalisa Ciabattini / Hassan Abolhassani / David Jarrossay / Mariagrazia Uguccioni / Donata Medaglini / Qiang Pan-Hammarström / Luigi Calzolai / Daniel Fernandez / Fausto Baldanti / Alessandra Franzetti-Pellanda / Christian Garzoni / Radislav Sedlacek / Daniel Ruzek / Luca Varani / Andrea Cavalli / Christopher O Barnes / Davide F Robbiani /
PubMed AbstractEmergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies ...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.
External linksSci Immunol / PubMed:36701425 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2 - 3.7 Å
Structure data

27177

8d48

EMDB-27177, PDB-8d48:
sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein
Method: EM (single particle) / Resolution: 3.7 Å

PDB-8d47:
fp.006 Fab in complex with SARS-CoV-2 Fusion Peptide
Method: X-RAY DIFFRACTION / Resolution: 2.0 Å

Chemicals

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER / Diethylene glycol

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-PO4:
PHOSPHATE ION / Phosphate

ChemComp-HOH:
WATER / Water

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsANTIVIRAL PROTEIN / antibody / fusion peptide / TMPRSS2 binding site / complex / SD1 / SARS-CoV-2

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