Computational refinement and multivalent engineering of complementarity-determining region-grafted nanobodies on a humanized scaffold for retaining antiviral efficacy.

ABSTRACT: Recently, nanobody-based therapeutics have emerged as a highly effective strategy for COVID-19 treatment. However, camelid-derived nanobodies often require humanization engineering to reduce immunogenicity in clinical applications while simultaneously preserving their target-binding affinities. Here, we employed a computational and engineering approach to optimize the binding affinities of complementarity-determining region (CDR)-grafted humanized variants of the camelid-derived nanobody Nb2-67, which exhibits potent SARS-CoV-2 neutralization. By grafting the three CDR loops of Nb2-67 onto the humanized scaffold of the approved therapeutic nanobody Caplacizumab and refining the target-binding interface, we generated five nanobody variants with improved computational humanness scores. Three

SUBMITTER: Huo L 

PROVIDER: S-EPMC12449085 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature