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Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants

التفاصيل البيبلوغرافية
العنوان: Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants
المؤلفون: Scott A. Hollingsworth, Cameron L. Noland, Karin Vroom, Anasuya Saha, Miranda Sam, Qinshan Gao, Haihong Zhou, David U. Grandy, Sujata Singh, Zhiyun Wen, Christopher Warren, Xiaohong Shirley Ma, Daniel Malashock, Jennifer Galli, Gwenny Go, Michael Eddins, Todd Mayhood, Karthik Sathiyamoorthy, Arthur Fridman, Fahimeh Raoufi, Yacob Gomez-Llorente, Andrea Patridge, Yinyan Tang, Shi-Juan Chen, Marc Bailly, Chengjie Ji, Laura J. Kingsley, Alan C. Cheng, Bernhard H. Geierstanger, Daniel M. Gorman, Lan Zhang, Kalyan Pande
المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-15 (2023)
بيانات النشر: Nature Portfolio, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Coronaviruses have been the causative agent of three epidemics and pandemics in the past two decades, including the ongoing COVID-19 pandemic. A broadly-neutralizing coronavirus therapeutic is desirable not only to prevent and treat COVID-19, but also to provide protection for high-risk populations against future emergent coronaviruses. As all coronaviruses use spike proteins on the viral surface to enter the host cells, and these spike proteins share sequence and structural homology, we set out to discover cross-reactive biologic agents targeting the spike protein to block viral entry. Through llama immunization campaigns, we have identified single domain antibodies (VHHs) that are cross-reactive against multiple emergent coronaviruses (SARS-CoV, SARS-CoV-2, and MERS). Importantly, a number of these antibodies show sub-nanomolar potency towards all SARS-like viruses including emergent CoV-2 variants. We identified nine distinct epitopes on the spike protein targeted by these VHHs. Further, by engineering VHHs targeting distinct, conserved epitopes into multi-valent formats, we significantly enhanced their neutralization potencies compared to the corresponding VHH cocktails. We believe this approach is ideally suited to address both emerging SARS-CoV-2 variants during the current pandemic as well as potential future pandemics caused by SARS-like coronaviruses.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-023-40919-7
URL الوصول: https://doaj.org/article/a9d7ab42a9cb4a6cb05bac47eef92301
رقم الأكسشن: edsdoj.9d7ab42a9cb4a6cb05bac47eef92301
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-023-40919-7