Camel nanobodies broadly neutralize SARS-CoV-2 variants.

ABSTRACT: With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V _H 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 ( Camelus dromedarius ) V _H H phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

SUBMITTER: Hong J 

PROVIDER: S-EPMC8575140 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature