tetano
Editor, Senior Moderator
PLoS Pathog
. 2023 Nov 30;19(11):e1011804.
doi: 10.1371/journal.ppat.1011804. eCollection 2023 Nov. Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization
Jing Yang[SUP] 1 [/SUP], Sheng Lin[SUP] 1 [/SUP], Zimin Chen[SUP] 1 [/SUP], Fanli Yang[SUP] 1 [/SUP], Liyan Guo[SUP] 1 [/SUP], Lingling Wang[SUP] 1 [/SUP], Yanping Duan[SUP] 1 [/SUP], Xindan Zhang[SUP] 1 [/SUP], Yushan Dai[SUP] 1 [/SUP], Keqing Yin[SUP] 1 [/SUP], Chongzhang Yu[SUP] 1 [/SUP], Xin Yuan[SUP] 1 [/SUP], Honglu Sun[SUP] 1 [/SUP], Bin He[SUP] 1 [/SUP], Yu Cao[SUP] 1 2 [/SUP], Haoyu Ye[SUP] 3 [/SUP], Haohao Dong[SUP] 4 [/SUP], Xianbo Liu[SUP] 5 [/SUP], Bo Chen[SUP] 5 [/SUP], Jian Li[SUP] 6 [/SUP], Qi Zhao[SUP] 7 [/SUP], Guangwen Lu[SUP] 1 [/SUP]
Affiliations
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.
. 2023 Nov 30;19(11):e1011804.
doi: 10.1371/journal.ppat.1011804. eCollection 2023 Nov. Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization
Jing Yang[SUP] 1 [/SUP], Sheng Lin[SUP] 1 [/SUP], Zimin Chen[SUP] 1 [/SUP], Fanli Yang[SUP] 1 [/SUP], Liyan Guo[SUP] 1 [/SUP], Lingling Wang[SUP] 1 [/SUP], Yanping Duan[SUP] 1 [/SUP], Xindan Zhang[SUP] 1 [/SUP], Yushan Dai[SUP] 1 [/SUP], Keqing Yin[SUP] 1 [/SUP], Chongzhang Yu[SUP] 1 [/SUP], Xin Yuan[SUP] 1 [/SUP], Honglu Sun[SUP] 1 [/SUP], Bin He[SUP] 1 [/SUP], Yu Cao[SUP] 1 2 [/SUP], Haoyu Ye[SUP] 3 [/SUP], Haohao Dong[SUP] 4 [/SUP], Xianbo Liu[SUP] 5 [/SUP], Bo Chen[SUP] 5 [/SUP], Jian Li[SUP] 6 [/SUP], Qi Zhao[SUP] 7 [/SUP], Guangwen Lu[SUP] 1 [/SUP]
Affiliations
- PMID: 38033141
- DOI: 10.1371/journal.ppat.1011804
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.