Evidence map›Paper›PMID 33082574›Full record

ArticleNature chemical biology2021

Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2.

Colton J Bracken, Shion A Lim, Paige Solomon, Nicholas J Rettko, Duy P Nguyen, Beth Shoshana Zha, Kaitlin Schaefer, James R Byrnes, Jie Zhou, Irene Lui and 6 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
–field-weighted citation impact
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

70 citing papers in PubMed.

  1. Trial
  2. Article
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  8. Article
  9. Article
  10. The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Article
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Colton J BrackenDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3499-7032
Shion A LimDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2136-2732
Paige SolomonDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Nicholas J RettkoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4332-2697
Duy P NguyenDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Beth Shoshana ZhaDepartment of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.
Kaitlin SchaeferDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
James R ByrnesDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0297-1209
Jie ZhouDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Irene LuiDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6171-5443
Jia LiuDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Katarina PanceDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
QCRG Structural Biology Consortium
Xin X ZhouDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Kevin K LeungDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2087-4974
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA. jim.wells@ucsf.edu.ORCID http://orcid.org/0000-0001-8267-5519

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
MUTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASEST32HL007185 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle, LAURENCE HUANG · 1985 to 2026
$24.6M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2018 to 2026
$21.4M
Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolutionR35GM122451 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2017 to 2026
$5.3M
Unveiling the Oncogenic Roles of ADAM10/17 by Comprehensively Profiling Proteolytic Activity on a Synthetic Human Protein Peptide Phage LibraryF32CA236151 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZHOU, JIE · 2019 to 2021
$195k
Characterizing and Targeting the Hypoxic T Cell Surfaceome to Promote Immune Function in CancerF32CA239417 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BYRNES, JAMES ROBERT · 2019 to 2021
$191k
Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) DRG-2204-14Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation) DRG-2297-17NCI NIH HHS F32 CA236151NCI NIH HHS F32 CA239417NHLBI NIH HHS T32 HL007185NIAID NIH HHS U19 AI135990NIGMS NIH HHS R35 GM122451NIGMS NIH HHS T32 GM007618United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) HR0011-19-2-0020U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5F32CA236151-02U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) F32 5F32CA239417U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) HL007185U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R35 GM122451-01
6 · The paper itself

Abstract

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC

Indexed as

Angiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralBinding Sites, AntibodyChlorocebus aethiopsCryoelectron MicroscopyHEK293 CellsHumansModels, MolecularPeptide LibraryProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSARS-CoV-2ACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralPeptide LibrarySingle-Chain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID33082574
PMCPMC8356808

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Registered trials

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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.