tetano
Editor, Senior Moderator
Small Methods
. 2022 May 18;e2200387.
doi: 10.1002/smtd.202200387. Online ahead of print.
A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape
Bo Feng[SUP] 1 2 [/SUP], Zhilong Chen[SUP] 3 4 [/SUP], Jing Sun[SUP] 1 [/SUP], Tingting Xu[SUP] 5 [/SUP], Qian Wang[SUP] 1 [/SUP], Haisu Yi[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Jiabin Zhu[SUP] 1 [/SUP], Mengzhu Fan[SUP] 3 [/SUP], Ruitian Hou[SUP] 5 [/SUP], Ying Shao[SUP] 3 [/SUP], Sihui Huang[SUP] 3 [/SUP], Cuiyun Li[SUP] 5 [/SUP], Peiyu Hu[SUP] 2 [/SUP], Pingqian Zheng[SUP] 2 [/SUP], Ping He[SUP] 5 [/SUP], Jia Luo[SUP] 4 [/SUP], Qihong Yan[SUP] 5 [/SUP], Xiaoli Xiong[SUP] 5 [/SUP], Jinsong Liu[SUP] 5 [/SUP], Jincun Zhao[SUP] 1 2 [/SUP], Ling Chen[SUP] 1 2 3 5 [/SUP]
Affiliations
Abstract
The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.
Keywords: SARS-CoV-2; neutralization; receptor binding domain (RBD); variants of concerns (VOCs).
. 2022 May 18;e2200387.
doi: 10.1002/smtd.202200387. Online ahead of print.
A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape
Bo Feng[SUP] 1 2 [/SUP], Zhilong Chen[SUP] 3 4 [/SUP], Jing Sun[SUP] 1 [/SUP], Tingting Xu[SUP] 5 [/SUP], Qian Wang[SUP] 1 [/SUP], Haisu Yi[SUP] 1 [/SUP], Xuefeng Niu[SUP] 1 [/SUP], Jiabin Zhu[SUP] 1 [/SUP], Mengzhu Fan[SUP] 3 [/SUP], Ruitian Hou[SUP] 5 [/SUP], Ying Shao[SUP] 3 [/SUP], Sihui Huang[SUP] 3 [/SUP], Cuiyun Li[SUP] 5 [/SUP], Peiyu Hu[SUP] 2 [/SUP], Pingqian Zheng[SUP] 2 [/SUP], Ping He[SUP] 5 [/SUP], Jia Luo[SUP] 4 [/SUP], Qihong Yan[SUP] 5 [/SUP], Xiaoli Xiong[SUP] 5 [/SUP], Jinsong Liu[SUP] 5 [/SUP], Jincun Zhao[SUP] 1 2 [/SUP], Ling Chen[SUP] 1 2 3 5 [/SUP]
Affiliations
- PMID: 35583124
- DOI: 10.1002/smtd.202200387
Abstract
The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.
Keywords: SARS-CoV-2; neutralization; receptor binding domain (RBD); variants of concerns (VOCs).