Deep Mutational Engineering of broadly-neutralizing and picomolar affinity nanobodies to accommodate SARS-CoV-1 & 2 antigenic polymorphism
Laroche, A.; Orsini Delgado, M. L.; Cuniasse, P.; Dubois, S.; Sierocki, R.; Gallais, F.; Debroas, S.; Bellanger, L.; Simon, S.; Maillere, B.; Nozach, H.
Show abstract
We report in this study the molecular engineering of nanobodies that bind with picomolar affinity to both SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domains (RBD) and are highly neutralizing. We applied Deep Mutational Engineering to VHH72, a nanobody initially specific for SARS-CoV-1 RBD with little cross-reactivity to SARS-CoV-2 antigen. We first identified all the individual VHH substitutions that increase binding to SARS-CoV-2 RBD and then screened highly focused combinatorial libraries to isolate engineered nanobodies with improved properties. The corresponding VHH-Fc molecules show high affinities for SARS-CoV-2 antigens from various emerging variants and SARS-CoV-1, block the interaction between ACE2 and RBD and neutralize the virus with high efficiency. Its rare specificity across sarbecovirus relies on its peculiar epitope outside the immunodominant regions. The engineered nanobodies share a common motif of three amino acids, which contribute to the broad specificity of recognition. These nanobodies appears as promising therapeutic candidates to fight SARS-CoV-2 infection.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface 97%
- Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain 97%
- Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2 97%
Similar papers in this journal
Similar papers in this journal
- Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration 95%
- No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor 95%
- Microtiter plate-based antibody-competition assay to determine binding affinities and plasma/blood stability of CXCR4 ligands 95%
Similar papers in this journal
- Conversion of an agonistic anti-TNFR2 biparatopic antibody into an antagonist by insertion of peptide linkers into the hinge region 96%
- Structure-guided stabilization improves the ability of the HIV-1 gp41 hydrophobic pocket to elicit neutralizing antibodies 96%
- Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment 95%
Similar papers in this journal
- Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody 96%
- Broad SARS-CoV-2 Neutralization by Monoclonal and Bispecific Antibodies Derived from a Gamma-infected Individual 95%
- Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.