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TitleSpike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery.
Journal, issue, pagesMol Ther, Vol. 31, Issue 2, Page 362-373, Year 2023
Publish dateSep 15, 2022
AuthorsFerdinando M Milazzo / Antonio Chaves-Sanjuan / Olga Minenkova / Daniela Santapaola / Anna M Anastasi / Gianfranco Battistuzzi / Caterina Chiapparino / Antonio Rosi / Emilio Merlo Pich / Claudio Albertoni / Emanuele Marra / Laura Luberto / Cécile Viollet / Luigi G Spagnoli / Anna Riccio / Antonio Rossi / M Gabriella Santoro / Federico Ballabio / Cristina Paissoni / Carlo Camilloni / Martino Bolognesi / Rita De Santis /
PubMed AbstractThe uneven worldwide vaccination coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of variants escaping immunity call for broadly effective and easily ...The uneven worldwide vaccination coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of variants escaping immunity call for broadly effective and easily deployable therapeutic agents. We have previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes the infectivity and fusogenic activity of the Omicron BA.1 and BA.2 variants. Cryoelectron microscopy (cryo-EM) analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope, providing the structural basis for its broad-spectrum activity. We demonstrate that nebulized scFv76 has therapeutic efficacy in a severe hACE2 transgenic mouse model of coronavirus disease 2019 (COVID-19) pneumonia, as shown by body weight and pulmonary viral load data. Counteraction of infection correlates with inhibition of lung inflammation, as observed by histopathology and expression of inflammatory cytokines and chemokines. Biomarkers of pulmonary endothelial damage were also significantly reduced in scFv76-treated mice. The results support use of nebulized scFv76 for COVID-19 induced by any SARS-CoV-2 variants that have emerged so far.
External linksMol Ther / PubMed:36114671 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 4.0 Å
Structure data

14628

7zce

EMDB-14628, PDB-7zce:
SARS-CoV-2 Spike protein in complex with the single chain fragment scFv76
Method: EM (single particle) / Resolution: 3.5 Å

14629

7zcf

EMDB-14629, PDB-7zcf:
SARS-CoV-2 Spike RBD in complex with the single chain fragment scFv76 (Focused Refinement)
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • enterobacteria phage t4 (virus)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike / single chain fragment

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