Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2
Tayeb-Fligelman, E.; Cheng, X.; Tai, C.; Bowler, J. T.; Griner, S.; Sawaya, M. R.; Seidler, P. M.; Jiang, Y. X.; Lu, J.; Rosenberg, G. M.; Salwinski, L.; Abskharon, R.; Zee, C.-T.; Hou, K.; Li, Y.; Boyer, D.; Murray, K. A.; Falcon, G.; Anderson, D. H.; Cascio, D.; Saelices, L.; Damoiseaux, R.; Guo, F.; Eisenberg, D.
Show 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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Development of an inhibitory TTC7B selective nanobody that blocks EFR3 recruitment of PI4KA 95%
- Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for receptor binding 95%
- Covalent inhibition of the SARS-CoV-2 NiRAN domain via an active-site cysteine 95%
Similar papers in this journal
Similar papers in this journal
- Quantitative Detection of Amyloid Fibrils using Fluorescence Resonance Energy Transfer (FRET) Between Engineered Yellow and Cyan Proteins 94%
- An evolutionarily conserved tryptophan cage promotes folding of the extended RNA recognition motif in the hnRNPR-like protein family 94%
- Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase 94%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.