Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection
The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP). Cryo-EM and biochemical data revealed that Nanosota-EB1 binds to the glycan cap of GP1, preventing its protease cleavage, while Nanosota-EB2 binds to critical membrane-fusion elements in GP2, stabilizing it in the pre-fusion state. Nanosota-EB2 is a potent neutralizer of EBOV infection in vitro and offers excellent protection in a mouse model of EBOV challenge, while Nanosota-EB1 provides moderate neutralization and protection. Nanosota-EB1 and Nanosota-EB2 are the first nanobodies shown to inhibit authentic EBOV. Combined with our newly developed structure-guided in vitro evolution approach, they lay the foundation for nanobody-based therapies against EBOV and other viruses within the ebolavirus genus.
Authors
- Bin Liu (ORCID: https://orcid.org/0000-0001-6485-7669)
- Benjamin W. Spiller (ORCID: https://orcid.org/0000-0001-5397-1028)
- Manu Anantpadma (ORCID: https://orcid.org/0000-0001-5796-532X)
- Robert A. Davey (ORCID: https://orcid.org/0000-0001-9168-2892)
- Alise Mendoza (ORCID: https://orcid.org/0000-0003-2966-8031)
- Brian E. Wadzinski (ORCID: https://orcid.org/0000-0002-2980-3697)
- Ge Yang (ORCID: https://orcid.org/0000-0002-0415-0933)
- Fan Bu (ORCID: https://orcid.org/0000-0002-6965-3072)
- Morgan Herbst
- Fang Li (ORCID: https://orcid.org/0000-0002-1958-366X)
- Gang Ye (ORCID: https://orcid.org/0000-0001-6034-2174)
- Kimberly M. Morsheimer
- Brett Eaton
- Hailey Turner‐Hubbard
Institutions
- Boston University (US)
- National Institutes of Health (US)
- University of Minnesota (US)
- Vanderbilt University (US)
- Hormel (United States) (US)
- National Institute of Allergy and Infectious Diseases (US)
- University of Minnesota Medical Center (US)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1371/journal.ppat.1012817
- Citations
- 3
- Primary Topic
- Viral Infections and Outbreaks Research
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases