Structural highlights
Function[NCAP_SARS2] Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. Publication Abstract from PubMedThe 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 Summary: Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics. Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2.,Tayeb-Fligelman E, Cheng X, Tai C, Bowler JT, Griner S, Sawaya MR, Seidler PM, Jiang YX, Lu J, Rosenberg GM, Salwinski L, Abskharon R, Zee CT, Hou K, Li Y, Boyer DR, Murray KA, Falcon G, Anderson DH, Cascio D, Saelices L, Damoiseaux R, Guo F, Eisenberg DS bioRxiv. 2021 Mar 5. doi: 10.1101/2021.03.05.434000. PMID:33688654[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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