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TitleCamel nanobodies broadly neutralize SARS-CoV-2 variants.
Journal, issue, pagesbioRxiv, Year 2021
Publish dateOct 29, 2021
AuthorsJessica Hong / Hyung Joon Kwon / Raul Cachau / Catherine Z Chen / Kevin John Butay / Zhijian Duan / Dan Li / Hua Ren / Tianyuzhou Liang / Jianghai Zhu / Venkata P Dandey / Negin Martin / Dominic Esposito / Uriel Ortega-Rodriguez / Miao Xu / Mario J Borgnia / Hang Xie / Mitchell Ho /
PubMed AbstractWith the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H nanobodies (7A3 and 8A2) from dromedary camels by phage display, ...With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of ≥5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants.
ONE-SENTENCE SUMMARY: Dromedary camel ( ) V H phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.
External linksbioRxiv / PubMed:34751270 / PubMed Central
MethodsEM (single particle)
Resolution2.39 Å
Structure data

26062

7tpr

EMDB-26062, PDB-7tpr:
Camel nanobodies 7A3 and 8A2 broadly neutralize SARS-CoV-2 variants
Method: EM (single particle) / Resolution: 2.39 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • camelus dromedarius (Arabian camel)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Neutralization / nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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