ArticlePloS one2022
A humanized nanobody phage display library yields potent binders of SARS CoV-2 spike.
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Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13citing papers in PubMed
1.4field-weighted citation impact, top 17% of its field
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Is faster always better? A critical assessment of Vibrio natriegens as microbial host for recombinant protein production.Bioprocess and biosystems engineering · 2026Review
- Nanobodies targeting SARS-CoV-2 variants.Acta pharmaceutica Sinica. B · 2026Review
- Engineered IgA-Fc fusion protein with bioactive nanobody neutralizes SARS-CoV-2 variants with mucosal delivery potential.The Journal of biological chemistry · 2026Article
- Nanobody engineering: computational modelling and design for biomedical and therapeutic applications.FEBS open bio · 2025Review
- Characterization of neutralizing chimeric heavy-chain antibodies against tetanus toxin.Human vaccines & immunotherapeutics · 2024Article
- Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.Journal of nanobiotechnology · 2024Review
- Producing recombinant proteins in Vibrio natriegens.Microbial cell factories · 2024Article
- Isolation and characterization of Hc-targeting chimeric heavy chain antibodies neutralizing botulinum neurotoxin type B.Frontiers in immunology · 2024Article
- Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19.Viruses · 2023Review
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
- The Potential of Nanobodies for COVID-19 Diagnostics and Therapeutics.Molecular diagnosis & therapy · 2023Review
- Applications of nanobodies in the prevention, detection, and treatment of the evolving SARS-CoV-2.Biochemical pharmacology · 2023Review
- Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
32 authors at 3 institutions in 1 country.
Ying FuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Juliana da Fonseca Rezende E MelloGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Bryan D FlemingNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.ORCID 0000-0003-3556-0852
Alex RennNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.ORCID 0000-0001-6320-9459
Catherine Z ChenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Xin HuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Miao XuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Kirill GorshkovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Quinlin HansonNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.ORCID 0000-0003-1034-0757
Emily M LeeNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Lalith PereraGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Robert PetrovichGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Manisha PradhanNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Richard T EastmanNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Zina ItkinNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Thomas B StanleyGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Allen HsuGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.ORCID 0000-0003-2065-3802
Venkata DandeyGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Kedar SharmaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.ORCID 0000-0002-6679-2341
William GilletteProtein Expression Laboratory, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Troy TaylorProtein Expression Laboratory, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Nitya RamakrishnanProtein Expression Laboratory, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Shelley PerkinsProtein Expression Laboratory, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Dominic EspositoProtein Expression Laboratory, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
Eunkeu OhOptical Sciences Division, Naval Research Laboratory, Washington, D.C., United States of America.ORCID 0000-0003-1641-522X
Kimihiro SusumuOptical Sciences Division, Naval Research Laboratory, Washington, D.C., United States of America.
Mason WolakOptical Sciences Division, Naval Research Laboratory, Washington, D.C., United States of America.
Marc FerrerNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
Matthew D HallNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.ORCID 0000-0002-5073-442X
Mario J BorgniaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America.
Anton SimeonovNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, United States of America.
National Institutes of Health · USProtein Express (United States) · USUnited States Naval Research Laboratory · US
Funding
Epitope dynamics of SARS-CoV-2 S protein by cryo-electron tomography and single particle cryo-EMZIAES103341 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BORGNIA, MARIO · 2020 to 2025
$3.9MMACROMOLECULAR MODELING AND CARCINOGENESISZ01ES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DARDEN, THOMAS A · 1986 to 2008
$1.2MDevelopment of a Robust Bioprocess to Rapidly Produce Griffithsin, a Broad-Spectrum Therapeutic and Preventive Antiviral CandidateZIATR000441 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WU, EDWARD · 2022 to 2025
$1.1MAntibody discoveryZIATR000394 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI SIMEONOV, ANTON · 2019 to 2023
$658kCCR NIH HHS HHSN261200800001CIntramural NIH HHS Z01 ES043010Intramural NIH HHS ZIA ES103341NCI NIH HHS HHSN261200800001E
Abstract
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.
Indexed as
BacteriophagesCOVID-19Single-Domain AntibodiesAntibodies, NeutralizingAntibodies, ViralHumansProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralSingle-Domain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.