other·infectious disease, immunology, preclinical research, public health·PMC10251734
A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants
iScience · 38 authors, 16 centres
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FIDELITY 100%
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A nanobody (W25) raised against the ancestral SARS-CoV-2 RBD was characterized by structural analysis and in vitro neutralization assays against multiple variants of concern, demonstrating potent neutralization of Omicron, Alpha, Beta, and Gamma. In K18-hACE2 mice, prophylactic W25-Fc provided full protection against a fatal SARS-CoV-2 challenge, and therapeutic intranasal delivery improved survival after Omicron infection.
Full summary
739 CHARS
In live-virus neutralization assays using Vero E6 cells, W25 and its Fc-fused dimer (W25-Fc) potently neutralized Omicron, Alpha, Beta, and Gamma variants, while neutralization of Kappa, Lambda, and Delta was strongly impeded, attributed to the L452R/Q mutation. W25 tolerates mutations at position 484, including E484K/A/Q. In K18-hACE2 transgenic mice, prophylactic W25-Fc administration before infection provided full protection from fatal challenge with no weight loss, and single-dose intranasal therapeutic delivery improved survival against both Beta and Omicron. Limitations include reliance on Vero E6 and HEK293-ACE2 overexpression cell lines rather than primary airway cells, and nebulization was only tested in uninfected mice.
