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针对 SARS-CoV-2 奥密克戎变体具有中和活性的纳米抗体的结构和功能表征。

Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2.

机构信息

Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK.

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford, UK.

出版信息

Open Biol. 2024 Jun;14(6):230252. doi: 10.1098/rsob.230252. Epub 2024 Jun 4.

DOI:10.1098/rsob.230252
PMID:38835241
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11285730/
Abstract

The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the 'arms race' with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.

摘要

SARS-CoV-2 的奥密克戎株给有效的基于抗体的治疗方法的开发带来了重大挑战，因为免疫逃逸使大多数可用的免疫疗法失效。因此，在与病毒的“军备竞赛”中，需要不断寻找预防或治疗 SARS-CoV-2 感染的新生物制剂。在这里，我们通过筛选先前用武汉或 Beta 刺突蛋白免疫的骆驼产生的纳米抗体噬菌体展示文库，报告了结合奥密克戎 BA.1 刺突蛋白的纳米抗体的分离。这三种纳米抗体（A8、H6 和 B5-5）的结构和结合特性已被详细表征，为它们在奥密克戎刺突蛋白上的结合表位提供了深入了解。H6 和 B5-5 的三聚体形式在鼻腔给药后中和了 SARS-CoV-2 的关注变体 BA.5 ，以及 COVID-19 的仓鼠模型。因此，单独或联合使用都可以作为开发新抗病毒免疫疗法的起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/cc8a4f1fe1d2/rsob.230252.f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/9bdaafbbd4cb/rsob.230252.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/88f10eb06e0a/rsob.230252.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/c71a1d870d63/rsob.230252.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/812de4f79bc3/rsob.230252.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/a31b0dce7886/rsob.230252.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/607698775cad/rsob.230252.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/cc8a4f1fe1d2/rsob.230252.f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/9bdaafbbd4cb/rsob.230252.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/88f10eb06e0a/rsob.230252.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/c71a1d870d63/rsob.230252.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/812de4f79bc3/rsob.230252.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/a31b0dce7886/rsob.230252.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/607698775cad/rsob.230252.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc1f/11285730/cc8a4f1fe1d2/rsob.230252.f007.jpg

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