Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2

doi:10.1126/science.abe4747

GSTDTAP > 气候变化

DOI	10.1126/science.abe4747
	Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2
	Yufei Xiang; Sham Nambulli; Zhengyun Xiao; Heng Liu; Zhe Sang; W. Paul Duprex; Dina Schneidman-Duhovny; Cheng Zhang; Yi Shi
	2020-12-18
发表期刊	Science
出版年	2020
英文摘要	Monoclonal antibodies that bind to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show therapeutic promise but must be produced in mammalian cells and need to be delivered intravenously. By contrast, single-domain antibodies called nanobodies can be produced in bacteria or yeast, and their stability may enable aerosol delivery. Two papers now report nanobodies that bind tightly to spike and efficiently neutralize SARS-CoV-2 in cells. Schoof et al. screened a yeast surface display of synthetic nanobodies and Xiang et al. screened anti-spike nanobodies produced by a llama. Both groups identified highly potent nanobodies that lock the spike protein in an inactive conformation. Multivalent constructs of selected nanobodies achieved even more potent neutralization. Science , this issue p. [1473][1], p. [1479][2] Cost-effective, efficacious therapeutics are urgently needed to combat the COVID-19 pandemic. In this study, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD). We discovered Nbs with picomolar to femtomolar affinities that inhibit viral infection at concentrations below the nanograms-per-milliliter level, and we determined a structure of one of the most potent Nbs in complex with the RBD. Structural proteomics and integrative modeling revealed multiple distinct and nonoverlapping epitopes and indicated an array of potential neutralization mechanisms. We bioengineered multivalent Nb constructs that achieved ultrahigh neutralization potency (half-maximal inhibitory concentration as low as 0.058 ng/ml) and may prevent mutational escape. These thermostable Nbs can be rapidly produced in bulk from microbes and resist lyophilization and aerosolization. [1]: /lookup/doi/10.1126/science.abe3255 [2]: /lookup/doi/10.1126/science.abe4747
领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/308370
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yufei Xiang,Sham Nambulli,Zhengyun Xiao,et al. Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2[J]. Science,2020.
APA	Yufei Xiang.,Sham Nambulli.,Zhengyun Xiao.,Heng Liu.,Zhe Sang.,...&Yi Shi.(2020).Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2.Science.
MLA	Yufei Xiang,et al."Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2".Science (2020).