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Publication Abstract from PubMed

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and Nb-021) that target non-overlapping epitopes in SARS-CoV-2 S-RBD. Both nanobodies could efficiently neutralize diverse viruses of SARS-CoV-2. The neutralizing mechanisms for the two nanobodies are further delineated by high-resolution nanobody/S-RBD complex structures. In addition, an Fc-based tetravalent nanobody format is constructed by combining Nb-015 and Nb-021. The resultant nanobody conjugate, designated as Nb-X2-Fc, exhibits significantly enhanced breadth and potency against all-tested SARS-CoV-2 variants, including Omicron sub-lineages. These data demonstrate that Nb-X2-Fc could serve as an effective drug candidate for the treatment of SARS-CoV-2 infection, deserving further in-vivo evaluations in the future.

Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization.,Yang J, Lin S, Chen Z, Yang F, Guo L, Wang L, Duan Y, Zhang X, Dai Y, Yin K, Yu C, Yuan X, Sun H, He B, Cao Y, Ye H, Dong H, Liu X, Chen B, Li J, Zhao Q, Lu G PLoS Pathog. 2023 Nov 30;19(11):e1011804. doi: 10.1371/journal.ppat.1011804. , eCollection 2023 Nov. PMID:38033141^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.