A multivalent nanobody-drug conjugate to prevent and treat influenza virus infections.

ABSTRACT: We describe the production and use of nanobody drug conjugates that comprise of VHH_kappa, a nanobody that recognizes mouse immunoglobulin kappa light chains, and one or more copies of the small molecule influenza virus neuraminidase (NA) inhibitor, zanamivir. Such compounds achieve half-life extension of zanamivir, while recruiting polyclonal immunoglobulins of all isotypes regardless of specificity to infected cells for antibody-dependent cell-mediated cytotoxicity and complement-dependent cellular cytotoxicity. Since the influenza A virus (IAV) NA is a tetramer, we produced VHH_kappa adducts with 1, 2, or 4 zanamivir molecules attached in a site-specific manner, to allow multivalent engagement of NA. Administration of a VHH_kappa adduct modified with 4 zana

SUBMITTER: Harmand TJ 

PROVIDER: S-EPMC12625891 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature