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针对亲和力启发疗法的抗严重急性呼吸综合征冠状病毒1和2纳米抗体工程。

Anti-SARS-CoV-1 and -2 nanobody engineering towards avidity-inspired therapeutics.

作者信息

Obeng Eugene M, Dzuvor Christian K O, Danquah Michael K

机构信息

Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.

Bioengineering Laboratory, Department of Chemical and Biological Engineering, Monash University, Clayton, VIC 3800, Australia.

出版信息

Nano Today. 2022 Feb;42:101350. doi: 10.1016/j.nantod.2021.101350. Epub 2021 Nov 23.

Abstract

In the past two decades, the emergence of coronavirus diseases has been dire distress on both continental and global fronts and has resulted in the search for potent treatment strategies. One crucial challenge in this search is the recurrent mutations in the causative virus spike protein, which lead to viral escape issues. Among the current promising therapeutic discoveries is the use of nanobodies and nanobody-like molecules. While these nanobodies have demonstrated high-affinity interaction with the virus, the unpredictable spike mutations have warranted the need for avidity-inspired therapeutics of potent inhibitors such as nanobodies. This article discusses novel approaches for the design of anti-SARS-CoV-1 and -2 nanobodies to facilitate advanced innovations in treatment technologies. It further discusses molecular interactions and suggests multivalent protein nanotechnology and chemistry approaches to translate mere molecular affinity into avidity.

摘要

在过去二十年中,冠状病毒疾病的出现给各大洲乃至全球都带来了严重困扰,并促使人们寻找有效的治疗策略。在这一探索过程中,一个关键挑战是致病病毒刺突蛋白的反复突变,这导致了病毒逃逸问题。目前有前景的治疗发现之一是使用纳米抗体和类纳米抗体分子。虽然这些纳米抗体已证明与病毒具有高亲和力相互作用,但不可预测的刺突突变使得有必要开发受亲和力启发的强效抑制剂(如纳米抗体)治疗方法。本文讨论了设计抗SARS-CoV-1和 -2纳米抗体的新方法,以促进治疗技术的进一步创新。文章还讨论了分子相互作用,并提出了多价蛋白质纳米技术和化学方法,以将单纯的分子亲和力转化为亲和力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a6d/8608585/ab9932025d2b/ga1_lrg.jpg

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