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Filename: controllers/Detail.php
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Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.
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Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365158 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0272364 | PLOS |
Int J Mol Sci
December 2024
Renal Medicine, Kolling Institute of Medical Research, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
Kidney fibrosis is the common pathological pathway in progressive chronic kidney disease (CKD), and current treatments are largely ineffective. The C-X-C chemokine receptor 4 (CXCR4) is crucial to fibrosis development. By using neural cell adhesion molecules as scaffolds with binding loops that mimic the shape of shark antibodies, fully humanized single-domain i-bodies have been developed.
View Article and Find Full Text PDFProtein Sci
November 2024
Antibody Discovery and Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany.
J Transl Med
October 2024
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
Background: BI 836880 is a humanized bispecific nanobody® that binds to and blocks vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2). A comprehensive biomarker and modeling approach is presented here that supported dose finding for BI 836880.
Methods: Two Phase I dose-escalation studies (1336.
Expert Opin Biol Ther
November 2024
Department of Gastroenterology, St Thomas' Hospital, London, UK.
Brief Bioinform
July 2024
Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, Pharmacometrics & System Pharmacology PharmacoAnalytics, School of Pharmacy, University of Pittsburgh, 335 Sutherland Drive, Pittsburgh, PA 15261, United States.
Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!