Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Synthetic nanobodies targeting the SARS-CoV-2 receptor-binding domain

Justin D. Walter, Cedric A.J. Hutter, Iwan Zimmermann, Jennifer Earp, Pascal Egloff, Michèle Sorgenfrei, Lea M. Hürlimann, Imre Gonda, Gianmarco Meier, Sille Remm, Sujani Thavarasah, Philippe Plattet, Markus A. Seeger
doi: https://doi.org/10.1101/2020.04.16.045419
Justin D. Walter
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cedric A.J. Hutter
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iwan Zimmermann
1Institute of Medical Microbiology, University of Zurich, Switzerland
2Linkster Therapeutics AG, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer Earp
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pascal Egloff
1Institute of Medical Microbiology, University of Zurich, Switzerland
2Linkster Therapeutics AG, Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michèle Sorgenfrei
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lea M. Hürlimann
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Imre Gonda
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gianmarco Meier
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sille Remm
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sujani Thavarasah
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philippe Plattet
3Division of Experimental and Clinical Research, Vetsuisse Faculty, University of Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus A. Seeger
1Institute of Medical Microbiology, University of Zurich, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: m.seeger@imm.uzh.ch
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has resulted in a global health and economic crisis of unprecedented scale. The high transmissibility of SARS-CoV-2, combined with a lack of population immunity and prevalence of severe clinical outcomes, urges the rapid development of effective therapeutic countermeasures. Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2. In an expeditious process taking only twelve working days, sybodies were selected entirely in vitro from three large combinatorial libraries, using ribosome and phage display. We obtained six strongly enriched sybody pools against the isolated RBD and identified 63 unique anti-RBD sybodies which also interact in the context of the full-length SARS-CoV-2 spike protein. It is anticipated that compact binders such as these sybodies could feasibly be developed into an inhalable drug that can be used as a convenient prophylaxis against COVID-19. Moreover, generation of polyvalent antivirals, via fusion of anti-RBD sybodies to additional small binders recognizing secondary epitopes, could enhance the therapeutic potential and guard against escape mutants. We present full sequence information and detailed protocols for the identified sybodies, as a freely accessible resource. This report will be updated as we further characterize the identified sybodies, in terms of affinities, scaled-up purification yields, and their potential to neutralize SARS-CoV-2 infections.

Competing Interest Statement

Iwan Zimmermann, Pascal Egloff and Markus A. Seeger are founders and shareholders of Linkster Therapeutics AG.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted April 18, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Synthetic nanobodies targeting the SARS-CoV-2 receptor-binding domain
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Synthetic nanobodies targeting the SARS-CoV-2 receptor-binding domain
Justin D. Walter, Cedric A.J. Hutter, Iwan Zimmermann, Jennifer Earp, Pascal Egloff, Michèle Sorgenfrei, Lea M. Hürlimann, Imre Gonda, Gianmarco Meier, Sille Remm, Sujani Thavarasah, Philippe Plattet, Markus A. Seeger
bioRxiv 2020.04.16.045419; doi: https://doi.org/10.1101/2020.04.16.045419
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Synthetic nanobodies targeting the SARS-CoV-2 receptor-binding domain
Justin D. Walter, Cedric A.J. Hutter, Iwan Zimmermann, Jennifer Earp, Pascal Egloff, Michèle Sorgenfrei, Lea M. Hürlimann, Imre Gonda, Gianmarco Meier, Sille Remm, Sujani Thavarasah, Philippe Plattet, Markus A. Seeger
bioRxiv 2020.04.16.045419; doi: https://doi.org/10.1101/2020.04.16.045419

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (3686)
  • Biochemistry (7774)
  • Bioengineering (5668)
  • Bioinformatics (21245)
  • Biophysics (10563)
  • Cancer Biology (8162)
  • Cell Biology (11915)
  • Clinical Trials (138)
  • Developmental Biology (6738)
  • Ecology (10388)
  • Epidemiology (2065)
  • Evolutionary Biology (13843)
  • Genetics (9694)
  • Genomics (13056)
  • Immunology (8123)
  • Microbiology (19956)
  • Molecular Biology (7833)
  • Neuroscience (42973)
  • Paleontology (318)
  • Pathology (1276)
  • Pharmacology and Toxicology (2256)
  • Physiology (3350)
  • Plant Biology (7208)
  • Scientific Communication and Education (1309)
  • Synthetic Biology (1999)
  • Systems Biology (5528)
  • Zoology (1126)