Publikationsdatenbank

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Rothenberger, Sylvia

Hurdiss, Daniel L.

Walser, Marcel

Malvezzi, Francesca

Mayor, Jennifer

Ryter, Sarah

Moreno, Hector

Liechti, Nicole

Bosshart, Andreas

Iss, Chloé

Calabro, Valérie

Cornelius, Andreas

Hospodarsch, Tanja

Neculcea, Alexandra

Looser, Thamar

Schlegel, Anja

Fontaine, Simon

Villemagne, Denis

Paladino, Maria

Schiegg, Dieter

Mangold, Susanne

Reichen, Christian

Radom, Filip

Kaufmann, Yvonne

Schaible, Doris

Schlegel, Iris

Zitt, Christof

Sigrist, Gabriel

Straumann, Marcel

Wolter, Julia

Comby, Marco

Sacarcelik, Feyza

Drulyte, Ieva

Lyoo, Heyrhyoung

Wang, Chunyan

Li, Wentao

Du, Wenjuan

Binz, H. Kaspar

Herrup, Rachel

Lusvarghi, Sabrina

Neerukonda, Sabari Nath

Vassell, Russell

Wang, Wei

Adler, Julia M. (WE 5)

Eschke, Kathrin (WE 5)

Nascimento, Mariana (WE 5)

Abdelgawad, Azza (WE 5)

Gruber, Achim D. (WE 12)

Bushe, Judith (WE 12)

Kershaw, Olivia (WE 12)

Knutson, Charles G.

Balavenkatraman, Kamal K.

Ramanathan, Krishnan

Wyler, Emanuel

Teixeira Alves, Luiz Gustavo

Lewis, Seth

Watson, Randall

Haeuptle, Micha A.

Zürcher, Alexander

Dawson, Keith M.

Steiner, Daniel

Weiss, Carol D.

Amstutz, Patrick

van Kuppeveld, Frank J. M.

Stumpp, Michael T.

Bosch, Berend-Jan

Engler, Olivier

Trimpert, Jakob (WE 5)

Quelle

Nature biotechnology : the science and business of biotechnology

Bandzählung: 40

Heftzählung: 12

Seiten: 1845 – 1854

ISSN: 1087-0156

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41587-022-01382-3

DOI: 10.1038/s41587-022-01382-3

Pubmed: 35864170

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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).