ArticleNature biotechnology2022
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.
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Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis.Microbiology spectrum · 2022Pooled it
- Structure-Guided Design of Proteomimetics Targeting the SARS-CoV-2 S-RBD/hACE2 Interface.Journal of medicinal chemistry · 2026Article
- Dual-mode ClfA-targeting DARPin biologics protect against diverse methicillin-resistantbioRxiv : the preprint server for biology · 2026Article
- Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes.iScience · 2025Article
- Engineering a Coiled-Coil Protein for DARPin Presentation as a Potent SARS-CoV-2 Therapeutic.Biomacromolecules · 2025Article
- Evolution-guided design of mini-protein for high-contrastActa pharmaceutica Sinica. B · 2025Article
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma.Science advances · 2025Article
- Functional Activity and Binding Specificity of Small Ankyrin Repeat Proteins Called Ankyrons Against SARS-CoV-2 Variants.The AAPS journal · 2025Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.Journal of the American Chemical Society · 2025Article
- Structure-based computational design of antibody mimetics: challenges and perspectives.FEBS open bio · 2025Review
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.bioRxiv : the preprint server for biology · 2024Article
- Diversity and structural-functional insights of alpha-solenoid proteins.Protein science : a publication of the Protein Society · 2024Review
- Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.Expert opinion on drug discovery · 2024Review
- Article
- Redesigning amino/carboxyl ends of DARPin G3 for high thermostability and production in tobacco transplastomic plants.Plant cell reports · 2024Article
- The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells.Cancer immunology research · 2024Article
- COVID-19 drug discovery and treatment options.Nature reviews. Microbiology · 2024Review
- The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study.Open forum infectious diseases · 2024Article
- Clinical development of antivirals against SARS-CoV-2 and its variants.Current research in microbial sciences · 2024Review
- Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives.Viruses · 2023Article
Corrections and comments
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Authors and funding
68 authors at 11 institutions in 4 countries.
Sylvia Rothenberger *Spiez Laboratory, Austrasse, Spiez, Switzerland.ORCID http://orcid.org/0000-0001-8633-2994
Daniel L Hurdiss *Department Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Marcel Walser *Molecular Partners AG, Zurich-Schlieren, Switzerland.
Francesca Malvezzi *Molecular Partners AG, Zurich-Schlieren, Switzerland.
Jennifer MayorSpiez Laboratory, Austrasse, Spiez, Switzerland.
Sarah RyterSpiez Laboratory, Austrasse, Spiez, Switzerland.
Hector MorenoInstitute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland.
Nicole LiechtiSpiez Laboratory, Austrasse, Spiez, Switzerland.ORCID http://orcid.org/0000-0003-4354-2419
Andreas BosshartMolecular Partners AG, Zurich-Schlieren, Switzerland.
Chloé IssMolecular Partners AG, Zurich-Schlieren, Switzerland.
Valérie CalabroMolecular Partners AG, Zurich-Schlieren, Switzerland.
Andreas CorneliusMolecular Partners AG, Zurich-Schlieren, Switzerland.
Tanja HospodarschMolecular Partners AG, Zurich-Schlieren, Switzerland.
Alexandra NeculceaMolecular Partners AG, Zurich-Schlieren, Switzerland.
Thamar LooserMolecular Partners AG, Zurich-Schlieren, Switzerland.
Anja SchlegelMolecular Partners AG, Zurich-Schlieren, Switzerland.
Simon FontaineMolecular Partners AG, Zurich-Schlieren, Switzerland.
Denis VillemagneMolecular Partners AG, Zurich-Schlieren, Switzerland.ORCID http://orcid.org/0000-0002-4465-364X
Maria PaladinoMolecular Partners AG, Zurich-Schlieren, Switzerland.
Dieter SchieggMolecular Partners AG, Zurich-Schlieren, Switzerland.
Susanne MangoldMolecular Partners AG, Zurich-Schlieren, Switzerland.
Christian ReichenMolecular Partners AG, Zurich-Schlieren, Switzerland.
Filip RadomMolecular Partners AG, Zurich-Schlieren, Switzerland.
Yvonne KaufmannMolecular Partners AG, Zurich-Schlieren, Switzerland.
Doris SchaibleMolecular Partners AG, Zurich-Schlieren, Switzerland.
Iris SchlegelMolecular Partners AG, Zurich-Schlieren, Switzerland.
Christof ZittMolecular Partners AG, Zurich-Schlieren, Switzerland.
Gabriel SigristMolecular Partners AG, Zurich-Schlieren, Switzerland.
Marcel StraumannMolecular Partners AG, Zurich-Schlieren, Switzerland.
Julia WolterMolecular Partners AG, Zurich-Schlieren, Switzerland.
Marco CombyMolecular Partners AG, Zurich-Schlieren, Switzerland.
Feyza SacarcelikMolecular Partners AG, Zurich-Schlieren, Switzerland.
Ieva DrulyteMaterials and Structural Analysis, Thermo Fisher Scientific, Eindhoven, Netherlands.
Heyrhyoung LyooDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.ORCID http://orcid.org/0000-0001-5806-9463
Chunyan WangDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Wentao LiDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Wenjuan DuDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
H Kaspar BinzBinz Biotech Consulting, Zug, Switzerland.ORCID http://orcid.org/0000-0003-0702-2280
Rachel HerrupLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Sabrina LusvarghiLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0003-1793-0450
Sabari Nath NeerukondaLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Russell VassellLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Wei WangLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Julia M AdlerFreie Universität Berlin, Institut für Virologie, Berlin, Germany.ORCID http://orcid.org/0000-0001-8147-0351
Kathrin EschkeFreie Universität Berlin, Institut für Virologie, Berlin, Germany.
Mariana NascimentoFreie Universität Berlin, Institut für Virologie, Berlin, Germany.
Azza AbdelgawadFreie Universität Berlin, Institut für Virologie, Berlin, Germany.
Achim D GruberFreie Universität Berlin, Institut für Tierpathologie, Berlin, Germany.
Judith BusheFreie Universität Berlin, Institut für Tierpathologie, Berlin, Germany.ORCID http://orcid.org/0000-0001-6103-3277
Olivia KershawFreie Universität Berlin, Institut für Tierpathologie, Berlin, Germany.
Charles G KnutsonNovartis Institutes for BioMedical Research, PK Sciences, Cambridge, MA, USA.
Kamal K BalavenkatramanNovartis Institutes for BioMedical Research, Preclinical Safety, Basel, Switzerland.
Krishnan RamanathanNovartis Pharma AG, Basel, Switzerland.
Emanuel WylerMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-9884-1806
Luiz Gustavo Teixeira AlvesMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Seth LewisMolecular Partners AG, Zurich-Schlieren, Switzerland.
Randall WatsonMolecular Partners AG, Zurich-Schlieren, Switzerland.
Micha A HaeuptleMolecular Partners AG, Zurich-Schlieren, Switzerland.
Alexander ZürcherMolecular Partners AG, Zurich-Schlieren, Switzerland.
Keith M DawsonMolecular Partners AG, Zurich-Schlieren, Switzerland.ORCID http://orcid.org/0000-0002-1770-291X
Daniel SteinerMolecular Partners AG, Zurich-Schlieren, Switzerland.
Carol D WeissLaboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-9965-1289
Patrick AmstutzMolecular Partners AG, Zurich-Schlieren, Switzerland.
Frank J M van KuppeveldDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Michael T StumppMolecular Partners AG, Zurich-Schlieren, Switzerland. info@molecularpartners.com.ORCID http://orcid.org/0000-0001-7356-2061
Berend-Jan BoschDepartment Biomolecular Health Sciences, Division Infectious Diseases & Immunology - Virology section, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-3864-232X
Olivier EnglerSpiez Laboratory, Austrasse, Spiez, Switzerland.ORCID http://orcid.org/0000-0002-8404-1496
Jakob TrimpertFreie Universität Berlin, Institut für Virologie, Berlin, Germany.ORCID http://orcid.org/0000-0003-1616-0810
Molecular Partners (Switzerland) · CHFreie Universität Berlin · DECenter for Biologics Evaluation and Research · USUtrecht University · NLSpiez Laboratory · CHMax Delbrück Center · DENovartis (Switzerland) · CHNovartis (United States) · USThermo Fisher Scientific (Netherlands) · NLUniversity of Applied Sciences Utrecht · NLUniversity of Lausanne · CH
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19).
Indexed as
COVID-19SARS-CoV-2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingCombined Antibody TherapeuticsCricetinaeCryoelectron MicroscopyDesigned Ankyrin Repeat ProteinsHumansRecombinant Fusion ProteinsAntibodies, MonoclonalAntibodies, NeutralizingCombined Antibody TherapeuticsDesigned Ankyrin Repeat ProteinsensovibepRecombinant Fusion Proteins
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