Literature collection of the CovAmInf workgroup.
Editors Joshua T. Berryman Abdul Mannan Baig Artemi Bendandi Daniel Bonhenry Mattheos A.G. Koffas
Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils (2023)
Einav Tayeb-Fligelman, Jeannette T. Bowler, Christen E. Tai, Michael R. Sawaya, Yi Xiao Jiang, Gustavo Garcia, Sarah L. Griner, Xinyi Cheng, Lukasz Salwinski, Liisa Lutter, Paul M. Seidler, Jiahui Lu, Gregory M. Rosenberg, Ke Hou, Romany Abskharon, Hope Pan, Chih-Te Zee, David R. Boyer, Yan Li, Daniel H. Anderson, Kevin A. Murray, Genesis Falcon, Duilio Cascio, Lorena Saelices, Robert Damoiseaux, Vaithilingaraja Arumugaswami, Feng Guo, David S. Eisenberg
DOI: 10.1038/s41467-023-37865-3 PubMed: 37185252
This is a substantial look at amyloid formation of the NCAP protein of SARS-CoV-2. NCAP is an RNA binding protein, so assembly is modified in the presence of (viral) RNA but can also function without RNA. Steric zipper crystal structures are prepared for three hexapeptide segments from NCAP, 179-GSQASS, 217-AALALL, and 243-GQTVTK; these are very typical structures of the kind that Eisenberg has produced for many other short peptide segments. A fibril-capping peptide was designed to disrupt assembly of the AALALL segment, and this was tested in cells and shown to disrupt viral replication. From this, and the fact that NCAP binds RNA, we can take the conclusion that amyloid self-assembly in NCAP is part of the process of collecting RNA for packaging: disrupting amyloid assembly impairs replication of the virus. The closing paragraphs of discussion section give some good context for amyloid assembly in viruses, relating SARS-CoV2 to other more or less famous but very interesting examples such as the Hendra virus (causing encephalitis), HSV-1, cytomegalovirus, varicella-zoster: all of these (apparently) form heteromeric amyloid complexes with human host protein. Further examples of amyloid-forming virus proteins (there are many) include avibirnavirus, adenovirus, SARS-CoV2 envelope protein, ORF6, OR10.... and over two million other examples....