Evidence map›Paper›PMID 34171229›Full record

ArticleCell chemical biology2021

Directed evolution of potent neutralizing nanobodies against SARS-CoV-2 using CDR-swapping mutagenesis.

Jennifer M Zupancic, Alec A Desai, John S Schardt, Ghasidit Pornnoppadol, Emily K Makowski, Matthew D Smith, Andrew A Kennedy, Mayara Garcia de Mattos Barbosa, Marilia Cascalho, Thomas M Lanigan and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Discovering Novel Therapeutic VbioRxiv : the preprint server for biology · 2026
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  8. Discovering novel therapeutic VFrontiers in immunology · 2026
    Article
  9. Article
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  11. Article
  12. Review
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  14. Backstage Heroes-Yeast in COVID-19 Research.International journal of molecular sciences · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Jennifer M ZupancicDepartment of Chemical Engineering, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Alec A DesaiDepartment of Chemical Engineering, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
John S SchardtDepartment of Chemical Engineering, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Ghasidit PornnoppadolDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Emily K MakowskiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Matthew D SmithDepartment of Chemical Engineering, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Andrew A KennedyDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Mayara Garcia de Mattos BarbosaDepartment of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Marilia CascalhoDepartment of Surgery, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
Thomas M LaniganDivision of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Andrew W TaiDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA; Medicine Service, Ann Arbor Veterans Administration Health System, Ann Arbor, MI, USA.
Peter M TessierDepartment of Chemical Engineering, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ptessier@umich.edu.
University of Michigan–Ann Arbor · USBioSurfaces (United States) · USVA Ann Arbor Healthcare System · US

Funding

The Center for HIV RNA Studies (CRNA)U54GM103297 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TELESNITSKY, ALICE · 2017 to 2018
$10.2M
Donor-specific B cells in Transplantation.R01AI151588 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASCALHO, MARILIA ISABEL, PLATT, JEFFREY L · 2020 to 2025
$2.7M
Design and Evolution of Polyvalent Domain Antibodies Specific for Tau AggregatesRF1AG059723 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANE, RAVI S., TESSIER, PETER M · 2018 to 2022
$2.4M
Mechanisms transducing insulin and insulin resistance in the hippocampusR01AG050598 · NIA · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI MCNAY, EWAN C · 2016 to 2020
$1.9M
Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregatesR35GM136300 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2020 to 2024
$1.5M
HIV-1 Genomic RNA IntegrityR21AI152865 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KIDD, JEFFREY M, TAI, ANDREW W. · 2020 to 2021
$429k
NIAID NIH HHS R01 AI151588NIAID NIH HHS R21 AI152865NIA NIH HHS R01 AG050598NIA NIH HHS RF1 AG059723NIGMS NIH HHS R35 GM136300NIGMS NIH HHS U54 GM103297
6 · The paper itself

Abstract

There is widespread interest in facile methods for generating potent neutralizing antibodies, nanobodies, and other affinity proteins against SARS-CoV-2 and related viruses to address current and future pandemics. While isolating antibodies from animals and humans are proven approaches, these methods are limited to the affinities, specificities, and functional activities of antibodies generated by the immune system. Here we report a surprisingly simple directed evolution method for generating nanobodies with high affinities and neutralization activities against SARS-CoV-2. We demonstrate that complementarity-determining region swapping between low-affinity lead nanobodies, which we discovered unintentionally but find is simple to implement systematically, results in matured nanobodies with unusually large increases in affinity. Importantly, the matured nanobodies potently neutralize both SARS-CoV-2 pseudovirus and live virus, and possess drug-like biophysical properties. We expect that our methods will improve in vitro nanobody discovery and accelerate the generation of potent neutralizing nanobodies against diverse coronaviruses.

Indexed as

AnimalsAntibodies, NeutralizingChlorocebus aethiopsComplementarity Determining RegionsEpitopesHEK293 CellsHumansMutagenesisSaccharomyces cerevisiaeSARS-CoV-2Single-Domain AntibodiesSpike Glycoprotein, CoronavirusVero CellsAntibodies, NeutralizingComplementarity Determining RegionsEpitopesSingle-Domain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ACE2affinityCOVID-19maturationnanobodyneutralizationRBDreceptor-binding domainspikeyeast

Identifiers

PMID34171229
PMCPMC8223476
OpenAlexW3173700036

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.