Evidence map›Paper›PMID 34916516›Full record

ArticleNature communications2021

Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography.

Obinna C Ubah, Eric W Lake, Gihan S Gunaratne, Joseph P Gallant, Marie Fernie, Austin J Robertson, Jonathan S Marchant, Tyler D Bold, Ryan A Langlois, William E Matchett and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

  1. Article
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  16. Article
  17. Identification of nurse shark VFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Obinna C Ubah *Elasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK.ORCID 0000-0001-9011-8405
Eric W Lake *Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
Gihan S Gunaratne *Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
Joseph P Gallant *Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
Marie FernieElasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK.
Austin J RobertsonDepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA.
Jonathan S MarchantDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.ORCID 0000-0001-6592-0877
Tyler D BoldDivision of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.
Ryan A LangloisCenter for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA.
William E MatchettCenter for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA.ORCID 0000-0001-7515-2226
Joshua M ThiedeDivision of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, MN, 55455, USA.ORCID 0000-0002-6603-281X
Ke ShiDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.
Lulu YinDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.
Nicholas H MoellerDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.
Surajit BanerjeeNortheastern Collaborative Access Team, Cornell University, Advanced Photon Source, Lemont, IL, 60439, USA.
Laura FergusonElasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK.
Marina KovalevaElasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK.
Andrew J PorterElasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK.
Hideki AiharaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA. aihar001@umn.edu.ORCID 0000-0001-7508-6230
Aaron M LeBeauDepartment of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53705, USA. aaron.lebeau@wisc.edu.ORCID 0000-0003-3802-7789
Caroline J BarelleElasmogen Ltd, Liberty Building Foresterhill Road, Aberdeen, AB25 2ZP, UK. caroline.barelle@elasmogen.com.ORCID 0000-0003-1872-3373

Funding

User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI MALCOLM S. CAPEL · 2018 to 2026
$34.2M
PROJECT 3 – BIOLOGY OF DNA DEAMINASES IN CANCERP01CA234228 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Reuben S Harris · 2019 to 2026
$14.5M
TRAINING-PULMONARY CELL &MOLECULAR BIOLOGY &PHYSIOLOGYT32HL007741 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DUDLEY, R. ADAMS, INGBAR, DAVID H · 1994 to 2023
$13.9M
Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Functional architecture of IP3-evoked local Ca2+ signalsR01GM088790 · NIGMS · UNIVERSITY OF MINNESOTA · PI MARCHANT, JONATHAN S, SLAMA, JAMES T · 2009 to 2025
$4.7M
Graduate Training in Molecular and Cellular PharmacologyT32GM141013 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anjon Audhya, Aaron Matthew LeBeau · 2021 to 2026
$3.2M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
Targeting CD133 for imaging and therapy in prostate cancerR01CA237272 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI LEBEAU, AARON MATTHEW · 2019 to 2023
$1.8M
Cyclic Peptide Protease Inhibitors for the Treatment of Prostate CancerR01CA245922 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI LEBEAU, AARON MATTHEW · 2020 to 2024
$1.7M
Novel Radioimmunotherapy Strategies for Prostate CancerR01CA233562 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI LEBEAU, AARON MATTHEW · 2019 to 2023
$1.7M
Chief Scientist Office COV/ABN/20/01NCI NIH HHS P01 CA234228NCI NIH HHS R01 CA233562NCI NIH HHS R01 CA237272NCI NIH HHS R01 CA245922NCRR NIH HHS S10 RR029205NHLBI NIH HHS T32 HL007741NIAID NIH HHS T32 AI055433NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM088790NIGMS NIH HHS R35 GM118047NIGMS NIH HHS T32 GM141013U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA233562U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA237272U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA245922
6 · The paper itself

Abstract

Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.

Indexed as

Crystallography, X-RayAngiotensin-Converting Enzyme 2AnimalsAntibodies, NeutralizingAntibodies, ViralCOVID-19EpitopesMutationPhylogenyProtein BindingReceptors, AntigenSARS-CoV-2Sequence AlignmentSharksSingle-Domain AntibodiesSpike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralEpitopesReceptors, AntigenSingle-Domain AntibodiesSpike Glycoprotein, Coronavirus

Identifiers

PMID34916516
PMCPMC8677774

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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.