The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.

Animals; Cricetinae; Humans; SARS-CoV-2/genetics; Designed Ankyrin Repeat Proteins; COVID-19; Cryoelectron Microscopy; Antibodies, Monoclonal/therapeutic use; Combined Antibody Therapeutics; Antibodies, Neutralizing

Sujets proches En

Analysis, Microscopic Optical microscopy Microscopic analysis Micrographic analysis Microscope and microscopy Light microscopy MAB Immune globulins Antibodies Immune serum globulin

Citer ce document

S. Rothenberger et al., « The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants. », Serveur académique Lausannois, ID : 10.1038/s41587-022-01382-3

Partage / Export

Résumé 0

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).

{"uri":"10.1038\/s41587-022-01382-3","creators":[{"id":"rothenberger_s.","lastname":"Rothenberger"},{"id":"hurdiss_d.l.","lastname":"Hurdiss"},{"id":"walser_m.","lastname":"Walser"},{"id":"malvezzi_f.","lastname":"Malvezzi"},{"id":"mayor_j.","lastname":"Mayor"},{"id":"ryter_s.","lastname":"Ryter"},{"id":"moreno_h.","lastname":"Moreno"},{"id":"liechti_n.","lastname":"Liechti"},{"id":"bosshart_a.","lastname":"Bosshart"},{"id":"iss_c.","lastname":"Iss"},{"id":"calabro_v.","lastname":"Calabro"},{"id":"cornelius_a.","lastname":"Cornelius"},{"id":"hospodarsch_t.","lastname":"Hospodarsch"},{"id":"neculcea_a.","lastname":"Neculcea"},{"id":"looser_t.","lastname":"Looser"},{"id":"schlegel_a.","lastname":"Schlegel"},{"id":"fontaine_s.","lastname":"Fontaine"},{"id":"villemagne_d.","lastname":"Villemagne"},{"id":"paladino_m.","lastname":"Paladino"},{"id":"schiegg_d.","lastname":"Schiegg"},{"id":"mangold_s.","lastname":"Mangold"},{"id":"reichen_c.","lastname":"Reichen"},{"id":"radom_f.","lastname":"Radom"},{"id":"kaufmann_y.","lastname":"Kaufmann"},{"id":"schaible_d.","lastname":"Schaible"},{"id":"schlegel_i.","lastname":"Schlegel"},{"id":"zitt_c.","lastname":"Zitt"},{"id":"sigrist_g.","lastname":"Sigrist"},{"id":"straumann_m.","lastname":"Straumann"},{"id":"wolter_j.","lastname":"Wolter"},{"id":"comby_m.","lastname":"Comby"},{"id":"sacarcelik_f.","lastname":"Sacarcelik"},{"id":"drulyte_i.","lastname":"Drulyte"},{"id":"lyoo_h.","lastname":"Lyoo"},{"id":"wang_c.","lastname":"Wang"},{"id":"li_w.","lastname":"Li"},{"id":"du_w.","lastname":"Du"},{"id":"binz_h.k.","lastname":"Binz"},{"id":"herrup_r.","lastname":"Herrup"},{"id":"lusvarghi_s.","lastname":"Lusvarghi"},{"id":"neerukonda_s.n.","lastname":"Neerukonda"},{"id":"vassell_r.","lastname":"Vassell"},{"id":"wang_w.","lastname":"Wang"},{"id":"adler_j.m.","lastname":"Adler"},{"id":"eschke_k.","lastname":"Eschke"},{"id":"nascimento_m.","lastname":"Nascimento"},{"id":"abdelgawad_a.","lastname":"Abdelgawad"},{"id":"gruber_a.d.","lastname":"Gruber"},{"id":"bushe_j.","lastname":"Bushe"},{"id":"kershaw_o.","lastname":"Kershaw"},{"id":"knutson_c.g.","lastname":"Knutson"},{"id":"balavenkatraman_k.k.","lastname":"Balavenkatraman"},{"id":"ramanathan_k.","lastname":"Ramanathan"},{"id":"wyler_e.","lastname":"Wyler"},{"id":"teixeira_alves_l.g.","lastname":"Teixeira Alves"},{"id":"lewis_s.","lastname":"Lewis"},{"id":"watson_r.","lastname":"Watson"},{"id":"haeuptle_m.a.","lastname":"Haeuptle"},{"id":"zurcher_a.","lastname":"Z\u00fcrcher"},{"id":"dawson_k.m.","lastname":"Dawson"},{"id":"steiner_d.","lastname":"Steiner"},{"id":"weiss_c.d.","lastname":"Weiss"},{"id":"amstutz_p.","lastname":"Amstutz"},{"id":"van_kuppeveld_fjm","lastname":"van Kuppeveld"},{"id":"stumpp_m.t.","lastname":"Stumpp"},{"id":"bosch_b.j.","lastname":"Bosch"},{"id":"engler_o.","lastname":"Engler"},{"id":"trimpert_j.","lastname":"Trimpert"}]}

Par les mêmes auteurs

{"uri":"10.1038\/s41587-022-01382-3","titles":["The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants."],"disciplines":[{"uri":"http:\/\/aurehal.archives-ouvertes.fr\/subject\/shs.eco","label":{"en":"Economies and finances","fr":"Economies et finances","es":"Econom\u00edas y finanzas"}}],"creators":[{"id":"rothenberger_s.","lastname":"Rothenberger"},{"id":"hurdiss_d.l.","lastname":"Hurdiss"},{"id":"walser_m.","lastname":"Walser"},{"id":"malvezzi_f.","lastname":"Malvezzi"},{"id":"mayor_j.","lastname":"Mayor"},{"id":"ryter_s.","lastname":"Ryter"},{"id":"moreno_h.","lastname":"Moreno"},{"id":"liechti_n.","lastname":"Liechti"},{"id":"bosshart_a.","lastname":"Bosshart"},{"id":"iss_c.","lastname":"Iss"},{"id":"calabro_v.","lastname":"Calabro"},{"id":"cornelius_a.","lastname":"Cornelius"},{"id":"hospodarsch_t.","lastname":"Hospodarsch"},{"id":"neculcea_a.","lastname":"Neculcea"},{"id":"looser_t.","lastname":"Looser"},{"id":"schlegel_a.","lastname":"Schlegel"},{"id":"fontaine_s.","lastname":"Fontaine"},{"id":"villemagne_d.","lastname":"Villemagne"},{"id":"paladino_m.","lastname":"Paladino"},{"id":"schiegg_d.","lastname":"Schiegg"},{"id":"mangold_s.","lastname":"Mangold"},{"id":"reichen_c.","lastname":"Reichen"},{"id":"radom_f.","lastname":"Radom"},{"id":"kaufmann_y.","lastname":"Kaufmann"},{"id":"schaible_d.","lastname":"Schaible"},{"id":"schlegel_i.","lastname":"Schlegel"},{"id":"zitt_c.","lastname":"Zitt"},{"id":"sigrist_g.","lastname":"Sigrist"},{"id":"straumann_m.","lastname":"Straumann"},{"id":"wolter_j.","lastname":"Wolter"},{"id":"comby_m.","lastname":"Comby"},{"id":"sacarcelik_f.","lastname":"Sacarcelik"},{"id":"drulyte_i.","lastname":"Drulyte"},{"id":"lyoo_h.","lastname":"Lyoo"},{"id":"wang_c.","lastname":"Wang"},{"id":"li_w.","lastname":"Li"},{"id":"du_w.","lastname":"Du"},{"id":"binz_h.k.","lastname":"Binz"},{"id":"herrup_r.","lastname":"Herrup"},{"id":"lusvarghi_s.","lastname":"Lusvarghi"},{"id":"neerukonda_s.n.","lastname":"Neerukonda"},{"id":"vassell_r.","lastname":"Vassell"},{"id":"wang_w.","lastname":"Wang"},{"id":"adler_j.m.","lastname":"Adler"},{"id":"eschke_k.","lastname":"Eschke"},{"id":"nascimento_m.","lastname":"Nascimento"},{"id":"abdelgawad_a.","lastname":"Abdelgawad"},{"id":"gruber_a.d.","lastname":"Gruber"},{"id":"bushe_j.","lastname":"Bushe"},{"id":"kershaw_o.","lastname":"Kershaw"},{"id":"knutson_c.g.","lastname":"Knutson"},{"id":"balavenkatraman_k.k.","lastname":"Balavenkatraman"},{"id":"ramanathan_k.","lastname":"Ramanathan"},{"id":"wyler_e.","lastname":"Wyler"},{"id":"teixeira_alves_l.g.","lastname":"Teixeira Alves"},{"id":"lewis_s.","lastname":"Lewis"},{"id":"watson_r.","lastname":"Watson"},{"id":"haeuptle_m.a.","lastname":"Haeuptle"},{"id":"zurcher_a.","lastname":"Z\u00fcrcher"},{"id":"dawson_k.m.","lastname":"Dawson"},{"id":"steiner_d.","lastname":"Steiner"},{"id":"weiss_c.d.","lastname":"Weiss"},{"id":"amstutz_p.","lastname":"Amstutz"},{"id":"van_kuppeveld_fjm","lastname":"van Kuppeveld"},{"id":"stumpp_m.t.","lastname":"Stumpp"},{"id":"bosch_b.j.","lastname":"Bosch"},{"id":"engler_o.","lastname":"Engler"},{"id":"trimpert_j.","lastname":"Trimpert"}]}

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants.

Fiche du document

Mots-clés 0

Sujets proches En

Citer ce document

Métriques

Partage / Export

Résumé 0

Par les mêmes auteurs

Sur les mêmes sujets

Sur les mêmes disciplines