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工程化的人类单克隆抗体对SARS样病毒具有广泛而有效的活性
作者:小柯机器人 发布时间:2021/1/26 17:04:14

近日,美国Adimab公司Laura M. Walker等研究人员合作发现,工程化的人类单克隆抗体对SARS样病毒具有广泛而有效的活性。相关论文于2021年1月25日在线发表在《科学》杂志上。

研究人员采用了定向进化方法来工程改造三种SARS-CoV-2抗体,从而提高了中和的广度和效力。亲和力成熟的一种变体(ADG-2)对大量的sarbecovirus受体结合结构域(RBD)表现出强大的结合活性,并能够以高效力来中和具有代表性的流行性sarbecoviruses。

结构和生化研究表明,ADG-2采用不同角度的方法来识别与受体结合位点重叠的高度保守表位。在具有免疫功能的SARS和COVID-19小鼠模型中,预防性给予ADG-2可提供针对呼吸负担、肺中病毒复制和肺部病理的全面保护。

总而言之,ADG-2是一种靶向sarbecovirus的潜在广谱治疗候选物。 

据悉,人群中冠状病毒(CoVs)感染的反复出现强调了广泛采取积极应对的必要性。

附:英文原文

Title: Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody

Author: C. Garrett Rappazzo, Longping V. Tse, Chengzi I. Kaku, Daniel Wrapp, Mrunal Sakharkar, Deli Huang, Laura M. Deveau, Thomas J. Yockachonis, Andrew S. Herbert, Michael B. Battles, Cecilia M. O’Brien, Michael E. Brown, James C. Geoghegan, Jonathan Belk, Linghang Peng, Linlin Yang, Yixuan Hou, Trevor D. Scobey, Dennis R. Burton, David Nemazee, John M. Dye, James E. Voss, Bronwyn M. Gunn, Jason S. McLellan, Ralph S. Baric, Lisa E. Gralinski, Laura M. Walker

Issue&Volume: 2021/01/25

Abstract: The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.

DOI: 10.1126/science.abf4830

Source: https://science.sciencemag.org/content/early/2021/01/22/science.abf4830

 

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