التفاصيل البيبلوغرافية
| العنوان: |
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants |
| المؤلفون: |
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, Eschke, Kathrin, Nascimento, Mariana, Abdelgawad, Azza, Gruber, Achim D, Bushe, Judith, Kershaw, Olivia, 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 |
| المساهمون: |
Virologie |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
Animals, Antibodies, Monoclonal/therapeutic use, Neutralizing, COVID-19, Combined Antibody Therapeutics, Cricetinae, Cryoelectron Microscopy, Designed Ankyrin Repeat Proteins, Humans, SARS-CoV-2/genetics |
| الوصف: |
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). |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1087-0156 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/425626 |
| الاتاحة: |
https://dspace.library.uu.nl/handle/1874/425626 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.AB8F7435 |
| قاعدة البيانات: |
BASE |