Journal article
Structure-guided in vitro evolution of nanobodies targeting new viral variants
PLoS pathogens, Vol.20(9), e1012600
09/26/2024
DOI: 10.1371/journal.ppat.1012600
PMCID: PMC11460708
PMID: 39325826
Abstract
A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies-single-domain antibodies derived from camelids-can be rapidly re-engineered to combat new viral strains through structure-guided in vitro evolution. Specifically, for viral mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select nanobody variants that effectively bind to the mutated viral target from a phage display library. As a proof of concept, we used this approach to adapt Nanosota-3, a nanobody originally identified to target the receptor-binding domain (RBD) of early Omicron subvariants, making it highly effective against recent Omicron subvariants. Remarkably, this adaptation process can be completed in less than two weeks, allowing drug development to keep pace with viral evolution and provide timely protection to humans.
Details
- Title: Subtitle
- Structure-guided in vitro evolution of nanobodies targeting new viral variants
- Creators
- Gang Ye - University of Minnesota Medical CenterFan Bu - University of Minnesota Medical CenterRuangang Pan - University of IowaAlise Mendoza - University of Minnesota Medical CenterGe Yang - HormelBenjamin Spiller - Vanderbilt UniversityBrian E Wadzinski - Vanderbilt UniversityLanying Du - Georgia State UniversityStanley Perlman - University of IowaBin Liu - HormelFang Li - University of Minnesota Medical Center
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.20(9), e1012600
- DOI
- 10.1371/journal.ppat.1012600
- PMID
- 39325826
- PMCID
- PMC11460708
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7374
- eISSN
- 1553-7374
- Publisher
- PUBLIC LIBRARY SCIENCE
- Grant note
- NIH: R01AI089728, R01AI157975, U19AI171954
This study was supported by funding from NIH grants R01AI089728 (to F.L.), R01AI157975 (to F.L., L.D., and S.P.), and U19AI171954 (to F.L., S.P., B.L., L.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Language
- English
- Date published
- 09/26/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984721139502771
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