V_HH antibody loop guides design of a synthetic macrocyclic peptide that potently blocks influenza virus membrane fusion.

ABSTRACT: Miniaturizing biologically complex structural motifs to produce synthetic functional mimetics holds significant promise for development of new therapeutic modalities. Here, we demonstrate a unique approach using the key binding loop of the single variable domain of a heavy chain (V_HH) llama antibody as a starting point for peptide design. V_HH antibodies of camelids and sharks generally have longer, but more ligand-efficient complementarity determining region 3 (CDR3) loops and are relatively stable structures. We harnessed these attributes as templates for design of a series of synthetic macrocyclic peptides. The designed peptides exhibit nanomolar binding to influenza hemagglutinin (HA) and heterosubtypic in vitro neutralization breadth against influenza A viruses by

SUBMITTER: Kadam RU 

PROVIDER: S-EPMC12714728 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature