Evidence map›Paper›PMID 35253970›Full record

ArticleEMBO reports2022

Biparatopic sybodies neutralize SARS-CoV-2 variants of concern and mitigate drug resistance.

Justin D Walter, Melanie Scherer, Cedric A J Hutter, Alisa A Garaeva, Iwan Zimmermann, Marianne Wyss, Jan Rheinberger, Yelena Ruedin, Jennifer C Earp, Pascal Egloff and 13 more

Open access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.2field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 44 citations in OpenAlex.

  1. Nanobodies targeting SARS-CoV-2 variants.Acta pharmaceutica Sinica. B · 2026
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  17. Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023
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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

23 authors at 3 institutions in 3 countries.

Justin D Walter *Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-1492-3055
Melanie Scherer *Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID 0000-0001-5554-9664
Cedric A J Hutter *Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-8920-3343
Alisa A Garaeva *Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-7394-8981
Iwan ZimmermannInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-3476-4749
Marianne WyssDivision of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID 0000-0002-2292-3282
Jan RheinbergerDepartment of Structural Biology at the Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-9901-2065
Yelena RuedinInstitute of Virology and Immunology, Bern & Mittelhäusern, Switzerland.ORCID 0000-0002-6852-6119
Jennifer C EarpInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-3944-4533
Pascal EgloffInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-8948-3704
Michèle SorgenfreiInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-8480-197X
Lea M HürlimannInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-9907-7830
Imre GondaInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-9951-181X
Gianmarco MeierInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-4455-430X
Sille RemmInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0001-5204-4556
Sujani ThavarasahInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-3957-2298
Geert van GeestInterfaculty Bioinformatics Unit and Swiss, Institute of Bioinformatics, University of Bern, Bern, Switzerland.ORCID 0000-0002-1561-078X
Rémy BruggmannInterfaculty Bioinformatics Unit and Swiss, Institute of Bioinformatics, University of Bern, Bern, Switzerland.ORCID 0000-0001-5629-6363
Gert ZimmerInstitute of Virology and Immunology, Bern & Mittelhäusern, Switzerland.ORCID 0000-0002-2708-2507
Dirk J SlotboomDepartment of Membrane Enzymology at the Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-5804-9689
Cristina PaulinoDepartment of Membrane Enzymology at the Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.ORCID 0000-0001-7017-109X
Philippe PlattetDivision of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bern, Switzerland.ORCID 0000-0003-3313-2598
Markus A SeegerInstitute of Medical Microbiology, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-1761-8571
University of Zurich · CHUniversity of Bern · CHUniversity of Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair, Sb#15 and Sb#68, that can bind simultaneously to the SARS-CoV-2 spike RBD and efficiently neutralize pseudotyped and live viruses by interfering with ACE2 interaction. Cryo-EM confirms that Sb#15 and Sb#68 engage two spatially discrete epitopes, influencing rational design of bispecific and tri-bispecific fusion constructs that exhibit up to 100- and 1,000-fold increase in neutralization potency, respectively. Cryo-EM of the sybody-spike complex additionally reveals a novel up-out RBD conformation. While resistant viruses emerge rapidly in the presence of single binders, no escape variants are observed in the presence of the bispecific sybody. The multivalent bispecific constructs further increase the neutralization potency against globally circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants.

Indexed as

COVID-19 Drug TreatmentSingle-Domain AntibodiesAntibodies, NeutralizingAntibodies, ViralDrug ResistanceHumansPandemicsProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralSingle-Domain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2escape mutantsSARS-CoV-2sybodiessynthetic nanobodiesvariants of concern

Identifiers

PMID35253970
PMCPMC8982573
OpenAlexW4221032617

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.