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Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2
Einav Tayeb-Fligelman; Xinyi Cheng; Christen Tai; Jeannette T. Bowler; Sarah Griner; Michael R. Sawaya; Paul M. Seidler; Yi Xiao Jiang; Jiahui Lu; Gregory M. Rosenberg; Lukasz Salwinski; Romany Abskharon; Chih-Te Zee; Ke Hou; Yan Li; David Boyer; Kevin A. Murray; Genesis Falcon; Daniel H. Anderson; Duilio Cascio; Lorena Saelices; Robert Damoiseaux; Feng Guo; David Eisenberg.
Afiliação
  • Einav Tayeb-Fligelman; University of California, Los Angeles
  • Xinyi Cheng; University of California Los Angeles (UCLA)
  • Christen Tai; University of California Los Angeles (UCLA)
  • Jeannette T. Bowler; University of California Los Angeles (UCLA)
  • Sarah Griner; University of California Los Angeles (UCLA)
  • Michael R. Sawaya; University of California Los Angeles (UCLA)
  • Paul M. Seidler; UCLA
  • Yi Xiao Jiang; University of California Los Angeles (UCLA)
  • Jiahui Lu; UCLA
  • Gregory M. Rosenberg; University of California Los Angeles (UCLA)
  • Lukasz Salwinski; UCLA
  • Romany Abskharon; University of California Los Angeles (UCLA)
  • Chih-Te Zee; University of California Los Angeles (UCLA)
  • Ke Hou; University of California Los Angeles (UCLA)
  • Yan Li; University of California Los Angeles (UCLA)
  • David Boyer; UCLA
  • Kevin A. Murray; University of California Los Angeles (UCLA)
  • Genesis Falcon; University of California Los Angeles (UCLA)
  • Daniel H. Anderson; University of California Los Angeles (UCLA)
  • Duilio Cascio; University of California Los Angeles (UCLA)
  • Lorena Saelices; University of California Los Angeles (UCLA)
  • Robert Damoiseaux; University of California Los Angeles (UCLA)
  • Feng Guo; University of California, Los Angeles
  • David Eisenberg; University of California Los Angeles (UCLA)
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-434000
ABSTRACT
The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19. One Sentence SummaryAtomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
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