Journal
PLOS ONE
Volume 17, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0272364
Keywords
-
Categories
Funding
- National Center for Advancing Translational Sciences (NCATS)
- NIH Intramural Targeted Anti-COVID-19 (ITAC) Program [ZIAES103341]
- National Institute of Environmental Health Sciences [ZICES10326, Z01ES043010]
- Intramural Research Program of the NIH
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- Naval Research Laboratory via its internal base program
- Cure Acceleration Network program at NCATS
Ask authors/readers for more resources
The study presents a rapid and efficient strategy for developing neutralizing humanized nanobody constructs against SARS-CoV-2. The most potent nanobody identified is capable of neutralizing the B.1.1.7 variant and withstands a specific mutation. Structural analysis and molecular dynamics simulations provide insights into the neutralization process. In an ex vivo model, the nanobody treatment effectively reduces viral burden for different SARS-CoV-2 strains.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available