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TitleDiscovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.
Journal, issue, pagesPLoS Pathog, Vol. 20, Issue 12, Page e1012817, Year 2024
Publish dateDec 23, 2024
AuthorsFan Bu / Gang Ye / Kimberly Morsheimer / Alise Mendoza / Hailey Turner-Hubbard / Morgan Herbst / Benjamin Spiller / Brian E Wadzinski / Brett Eaton / Manu Anantpadma / Ge Yang / Bin Liu / Robert Davey / Fang Li /
PubMed AbstractThe 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 ...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.
External linksPLoS Pathog / PubMed:39715280 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.36 Å
Structure data

44872

9bsu

EMDB-44872, PDB-9bsu:
EBOV GP/Nanosota-EB1
Method: EM (single particle) / Resolution: 3.36 Å

44873

9bsv

EMDB-44873, PDB-9bsv:
EBOV GP/Nanosota-EB2 complex
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-MAN:
alpha-D-mannopyranose

Source
  • ebola virus
  • vicugna pacos (alpaca)
KeywordsVIRAL PROTEIN / EBOV glycoprotein / nanobody

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