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A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein
Vito Thijssen; Daniel L. Hurdiss; Oliver J Debski-Antoniak; Matthew A Spence; Charlotte Franck; Alexander Norman; Anupriya Aggarwal; Nadia J Mokiem; David A A van Dongen; Stein W Vermeir; Minglong Liu; Marianthi Chatziandreou; Tim Donselaar; Wenjuan Du; Ieva Drulyte; Berend Jan Bosch; Joost Snijder; Stuart Grant Turville; Richard J Payne; Colin J Jackson; Frank J.M. van Kuppeveld; Seino A K Jongkees.
Afiliação
  • Vito Thijssen; Utrecht University, Vrije Universiteit Amsterdam
  • Daniel L. Hurdiss; Utrecht University
  • Oliver J Debski-Antoniak; Utrecht University
  • Matthew A Spence; Australian National University
  • Charlotte Franck; University of Sydney
  • Alexander Norman; University of Sydney
  • Anupriya Aggarwal; Kirby Institute
  • Nadia J Mokiem; Utrecht University
  • David A A van Dongen; Utrecht University, Vrije Universiteit Amsterdam
  • Stein W Vermeir; Universiteit Utrecht, Vrije Universiteit Amsterdam
  • Minglong Liu; Utrecht University, Vrije Universiteit Amsterdam
  • Marianthi Chatziandreou; Utrecht University
  • Tim Donselaar; Utrecht University
  • Wenjuan Du; Utrecht University
  • Ieva Drulyte; Thermo Fisher Scientific
  • Berend Jan Bosch; Utrecht University
  • Joost Snijder; Utrecht University
  • Stuart Grant Turville; Kirby Institute
  • Richard J Payne; The University of Sydney
  • Colin J Jackson; Australian National University
  • Frank J.M. van Kuppeveld; Utrecht University
  • Seino A K Jongkees; Vrije Universiteit Amsterdam
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-516114
ABSTRACT
The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection and also pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor binding domain and other domains, distal to the ACE2 receptor-interaction site. Collectively, our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that can be targeted by peptides and potentially other drug-like molecules. One-Sentence SummaryWe identify a conserved site on the SARS-CoV-2 spike that can be targeted by a broadly neutralizing macrocyclic peptide.
Licença
cc_by_nc_nd
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
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