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新型高效纳米抗体可用于中和SARS-CoV-2
作者:小柯机器人 发布时间:2020/11/8 22:05:52

美国匹兹堡大学Yi Shi等研究人员合作开发出新型高效纳米抗体用于中和SARS-CoV-2。2020年11月5日,《科学》杂志在线发表了这项成果。

研究人员使用了骆驼科动物免疫和蛋白质组学来鉴定了与SARS-CoV-2突刺(S)蛋白受体结合结构域(RBD)高度结合的强效中和纳米抗体(Nb)。研究人员发现了皮摩尔至飞摩尔亲和力的Nb,可在亚ng/ml浓度下抑制病毒感染,并确定了与RBD结合的最有效结构之一。结构蛋白质组学和整合建模揭示了多个不同且不重叠的表位,并表明了一系列潜在的中和机制。
 
研究人员构建了多价Nb框架,从而实现了超高的中和效能(IC50低至0.058ng/ml),并且可以防止突变逃逸。这些热稳定的Nb可以快速从微生物中大量产生,并且可以抵抗冻干和雾化。
 
附:英文原文

Title: Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2

Author: Yufei Xiang, Sham Nambulli, Zhengyun Xiao, Heng Liu, Zhe Sang, W. Paul Duprex, Dina Schneidman-Duhovny, Cheng Zhang, Yi Shi

Issue&Volume: 2020/11/05

Abstract: AbstractCost-effective, efficacious therapeutics are urgently needed against the COVID-19 pandemic. Here, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). We discovered Nbs with picomolar to femtomolar affinities that inhibit viral infection at sub-ng/ml concentration and determined a structure of one of the most potent in complex with RBD. Structural proteomics and integrative modeling revealed multiple distinct and non-overlapping epitopes and indicated an array of potential neutralization mechanisms. We constructed multivalent Nb constructs that achieved ultrahigh neutralization potency (IC50s 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.

DOI: 10.1126/science.abe4747

Source: https://science.sciencemag.org/content/early/2020/11/04/science.abe4747

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037