SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation

doi:10.1007/s13238-022-00905-7

Protein Cell

2022, Vol. 13

Issue (8) : 602-614 https://doi.org/10.1007/s13238-022-00905-7

RESEARCH ARTICLE

SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation

Yichen Li^1,², Shuaiyao Lu^3,⁴, Jinge Gu^6,⁷, Wencheng Xia^6,⁷, Shengnan Zhang^6,⁷, Shenqing Zhang^1,², Yan Wang⁸, Chong Zhang⁸, Yunpeng Sun^6,⁷, Jian Lei⁸, Cong Liu^6,⁷, Zhaoming Su⁸(

), Juntao Yang⁵(

), Xiaozhong Peng^3,⁴(

), Dan Li^1,^9,¹⁰(

)

¹. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, China
². School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
³. National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650031, China
⁴. State Key Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
⁵. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
⁶. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
⁷. University of Chinese Academy of Sciences, Beijing 100049, China
⁸. State Key Laboratory of Biotherapy, Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China
⁹. Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
¹⁰. Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China

Download: PDF(5651 KB)
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.

Keywords SARS-CoV-2 nucleocapsid protein stress granule

Corresponding Author(s): Zhaoming Su,Juntao Yang,Xiaozhong Peng,Dan Li

Issue Date: 27 July 2022

Cite this article:

Yichen Li,Shuaiyao Lu,Jinge Gu, et al. SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation[J]. Protein Cell, 2022, 13(8): 602-614.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-022-00905-7
https://academic.hep.com.cn/pac/EN/Y2022/V13/I8/602

1	R Amraei, W Yin, MA Napoleon, EL Suder, J Berrigan, Q Zhao, J Olejnik, K Chandler, C Xia, J Feldman, et al (2021) CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. bioRxiv
2	J Bellmann, A Monette, V Tripathy, A Sojka, M Abo-Rady, A Janosh, R Bhatnagar, M Bickle, AJ Mouland, J Sterneckert (2019) Viral infections exacerbate FUS-ALS phenotypes in iPSC-derived spinal neurons in a virus species-specific manner. Front Cell Neurosci 13: 480 https://doi.org/10.3389/fncel.2019.00480
3	M Bostanciklioglu (2020) Severe acute respiratory syndrome coronavirus 2 is penetrating to dementia research. Curr Neurovasc Res.
4	JR Buchan, RM Kolaitis, JP Taylor, R Parker (2013) Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell 153: 1461- 1474 https://doi.org/10.1016/j.cell.2013.05.037
5	KA Burke, AM Janke, CL Rhine, NL Fawzi (2015) Residue-by-residue view of in vitro FUS granules that bind the C-terminal domain of RNA polymerase Ⅱ. Mol Cell 60: 231- 241 https://doi.org/10.1016/j.molcel.2015.09.006
6	CR Carlson, JB Asfaha, CM Ghent, CJ Howard, N Hartooni, M Safari, AD Frankel, DO Morgan (2020) Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions. Mol Cell 80: 1092- 1103 https://doi.org/10.1016/j.molcel.2020.11.025
7	JF Chan, KH Kok, Z Zhu, H Chu, KK To, S Yuan, KY Yuen (2020) Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 9: 221- 236 https://doi.org/10.1080/22221751.2020.1719902
8	H Chen, Y Cui, X Han, W Hu, M Sun, Y Zhang, PH Wang, G Song, W Chen, J Lou (2020) Liquid-liquid phase separation by SARS-CoV-2 nucleocapsid protein and RNA. Cell Res 30: 1143- 1145 https://doi.org/10.1038/s41422-020-00408-2
9	J Chen, J Fan, Z Chen, M Zhang, H Peng, J Liu, L Ding, M Liu, C Zhao, P Zhao et al (2021) Nonmuscle myosin heavy chain IIA facilitates SARS-CoV-2 infection in human pulmonary cells. Proc Natl Acad Sci USA 118: e2111011118 https://doi.org/10.1073/pnas.2111011118
10	ME Cohen, R Eichel, B Steiner-Birmanns, A Janah, M Ioshpa, R Bar-Shalom, JJ Paul, H Gaber, V Skrahina, NM Bornstein et al (2020) A case of probable Parkinson’s disease after SARS-CoV-2 infection. Lancet Neurol 19: 804- 805 https://doi.org/10.1016/S1474-4422(20)30305-7
11	AE Conicella, GH Zerze, J Mittal, NL Fawzi (2016) ALS mutations disrupt phase separation mediated by alpha-helical structure in the TDP-43 low-complexity C-terminal domain. Structure 24: 1537- 1549 https://doi.org/10.1016/j.str.2016.07.007
12	F Crunfli, VC Carregari, FP Veras, PH Vendramini, AG Fragnani Valença, ASL Marcelo Antunes, C Brandão-Teles, G da Silva Zuccoli, G Reis-de-Oliveira, LC Silva-Costa, et al (2021) SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability. medRxiv
13	J Cubuk, JJ Alston, JJ Incicco, S Singh, MD Stuchell-Brereton, MD Ward, MI Zimmerman, N Vithani, D Griffith, JA Wagoner, et al (2020) The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. bioRxiv
14	R De Santis, V Alfano, V de Turris, A Colantoni, L Santini, MG Garone, G Antonacci, G Peruzzi, E Sudria-Lopez, E Wyler et al (2019) Mutant FUS and ELAVL4 (HuD) aberrant crosstalk in amyotrophic lateral sclerosis. Cell Rep 27: 3818- 3831 https://doi.org/10.1016/j.celrep.2019.05.085
15	D Dormann, R Rodde, D Edbauer, E Bentmann, I Fischer, A Hruscha, ME Than, IR Mackenzie, A Capell, B Schmid et al (2010) ALS-associated fused in sarcoma (FUS) mutations disrupt transportinmediated nuclear import. EMBO J 29: 2841- 2857 https://doi.org/10.1038/emboj.2010.143
16	Y Duan, A Du, J Gu, G Duan, C Wang, X Gui, Z Ma, B Qian, X Deng, K Zhang et al (2019) PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins. Cell Res 29: 233- 247 https://doi.org/10.1038/s41422-019-0141-z
17	WA Eimer, DK Vijaya Kumar, NK Navalpur Shanmugam, AS Rodriguez, T Mitchell, KJ Washicosky, B Gyorgy, XO Breakefield, RE Tanzi, RD Moir (2018) Alzheimer’s disease-associated beta-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron 99: 56- 63 https://doi.org/10.1016/j.neuron.2018.06.030
18	C Gao, J Zeng, N Jia, K Stavenhagen, Y Matsumoto, H Zhang, J Li, AJ Hume, E Muhlberger, Die I van, et al (2020) SARS-CoV-2 spike protein interacts with multiple innate immune receptors. bioRxiv
19	EM Gatto, J Fernandez Boccazzi (2020) COVID-19 and neurodegeneration: what can we learn from the past? Eur J Neurol. https://doi.org/10.1111/ene.14311
20	DE Gordon, GM Jang, M Bouhaddou, J Xu, K Obernier, KM White, MJ O’Meara, VV Rezelj, JZ Guo, DL Swaney et al (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583: 459- 468 https://doi.org/10.1038/s41586-020-2286-9
21	J Gu, C Wang, R Hu, Y Li, S Zhang, Y Sun, Q Wang, D Li, Y Fang, C Liu (2021a) Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation. Cell Res 31: 1024- 1027 https://doi.org/10.1038/s41422-021-00526-5
22	Y Gu, J Cao, X Zhang, H Gao, Y Wang, J Wang, J He, X Jiang, J Zhang, G Shen, et al (2021b) Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. Cell Res
23	S Guseva, S Milles, MR Jensen, N Salvi, JP Kleman, D Maurin, RWH Ruigrok, M Blackledge (2020) Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly. Sci Adv 6: eaaz7095 https://doi.org/10.1126/sciadv.aaz7095
24	Y Gwon, BA Maxwell, RM Kolaitis, P Zhang, HJ Kim, JP Taylor (2021) Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. Science 372: eabf6548 https://doi.org/10.1126/science.abf6548
25	ER Hascup, KN Hascup (2020) Does SARS-CoV-2 infection cause chronic neurological complications? Geroscience 42: 1083- 1087 https://doi.org/10.1007/s11357-020-00207-y
26	MT Heneka, D Golenbock, E Latz, D Morgan, R Brown (2020) Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther 12: 69 https://doi.org/10.1186/s13195-020-00640-3
27	C Iserman, CA Roden, MA Boerneke, RSG Sealfon, GA McLaughlin, I Jungreis, EJ Fritch, YJ Hou, J Ekena, CA Weidmann et al (2020) Genomic RNA elements drive phase separation of the SARS-CoV-2 nucleocapsid. Mol Cell 80: 1078- 1091 https://doi.org/10.1016/j.molcel.2020.11.041
28	S Jain, JR Wheeler, RW Walters, A Agrawal, A Barsic, R Parker (2016) ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164: 487- 498 https://doi.org/10.1016/j.cell.2015.12.038
29	H Jang, D Boltz, K Sturm-Ramirez, KR Shepherd, Y Jiao, R Webster, RJ Smeyne (2009) Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc Natl Acad Sci USA 106: 14063- 14068 https://doi.org/10.1073/pnas.0900096106
30	BS Johnson, D Snead, JJ Lee, JM McCaffery, J Shorter, AD Gitler (2009) TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J Biol Chem 284: 20329- 20339 https://doi.org/10.1074/jbc.M109.010264
31	M Kato, TW Han, S Xie, K Shi, X Du, LC Wu, H Mirzaei, EJ Goldsmith, J Longgood, J Pei et al (2012) Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149: 753- 767 https://doi.org/10.1016/j.cell.2012.04.017
32	R Kaur, SK Lal (2020) The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections. Rev Med Virol 30: e2097
33	HJ Kim, NC Kim, YD Wang, EA Scarborough, J Moore, Z Diaz, KS MacLea, B Freibaum, S Li, A Molliex et al (2013) Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495: 467- 473 https://doi.org/10.1038/nature11922
34	T Klingstedt, H Shirani, KO Aslund, NJ Cairns, CJ Sigurdson, M Goedert, KP Nilsson (2013) The structural basis for optimal performance of oligothiophene-based fluorescent amyloid ligands: conformational flexibility is essential for spectral assignment of a diversity of protein aggregates. Chemistry 19: 10179- 10192 https://doi.org/10.1002/chem.201301463
35	TJ Jr Kwiatkowski, DA Bosco, AL Leclerc, E Tamrazian, CR Vanderburg, C Russ, A Davis, J Gilchrist, EJ Kasarskis, T Munsat (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323: 1205- 1208 https://doi.org/10.1126/science.1166066
36	MM Lai, D Cavanagh (1997) The molecular biology of coronaviruses. Adv Virus Res 48: 1- 100
37	IC Lee, TI Huo, YH Huang (2020) Gastrointestinal and liver manifestations in patients with COVID-19. J Chin Med Assoc 83: 521- 523 https://doi.org/10.1097/JCMA.0000000000000319
38	W Li, MJ Moore, N Vasilieva, J Sui, SK Wong, MA Berne, M Somasundaran, JL Sullivan, K Luzuriaga, TC Greenough et al (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426: 450- 454 https://doi.org/10.1038/nature02145
39	H Li, Q Xue, X Xu (2020) Involvement of the nervous system in SARS-CoV-2 infection. Neurotox Res 38: 1- 7 https://doi.org/10.1007/s12640-020-00219-8
40	Z Liu, S Zhang, J Gu, Y Tong, Y Li, X Gui, H Long, C Wang, C Zhao, J Lu et al (2020) Hsp27 chaperones FUS phase separation under the modulation of stress-induced phosphorylation. Nat Struct Mol Biol 27: 363- 372 https://doi.org/10.1038/s41594-020-0399-3
41	L Luo, Z Li, P Ma, Y Zou, P Li, A Liang, Z Jin, T Chi, C Huang, Y Zhang, et al (2020) . SARS-CoV-2 Nucleocapsid protein impairs SG assembly by partitioning into G3BP condensate. SSRN Electron J
42	L Luo, Z Li, T Zhao, X Ju, P Ma, B Jin, Y Zhou, S He, J Huang, X Xu et al (2021a) SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble stress granules and facilitate viral production. Sci Bull 66: 1194- 1204 https://doi.org/10.1016/j.scib.2021.01.013
43	L Luo, Z Li, T Zhao, X Ju, P Ma, B Jin, Y Zhou, S He, J Huang, X Xu et al (2021b) SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble stress granules and facilitate viral production. Sci Bull 66 (12): 1194- 1204 https://doi.org/10.1016/j.scib.2021.01.013
44	L Mao, H Jin, M Wang, Y Hu, S Chen, Q He, J Chang, C Hong, Y Zhou, D Wang et al (2020) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan. China. JAMA Neurol 77 (6): 683- 690 https://doi.org/10.1001/jamaneurol.2020.1127
45	R Marreiros, A Muller-Schiffmann, SV Trossbach, I Prikulis, S Hansch, S Weidtkamp-Peters, AR Moreira, S Sahu, I Soloviev, S Selvarajah et al (2020) Disruption of cellular proteostasis by H1N1 influenza A virus causes alpha-synuclein aggregation. Proc Natl Acad Sci USA 117: 6741- 6751 https://doi.org/10.1073/pnas.1906466117
46	J Matschke, M Lutgehetmann, C Hagel, JP Sperhake, AS Schroder, C Edler, H Mushumba, A Fitzek, L Allweiss, M Dandri et al (2020) Neuropathology of patients with COVID-19 in Germany: a postmortem case series. Lancet Neurol 19: 919- 929 https://doi.org/10.1016/S1474-4422(20)30308-2
47	R McBride, Zyl M van, BC Fielding (2014) The coronavirus nucleocapsid is a multifunctional protein. Viruses 6: 2991- 3018 https://doi.org/10.3390/v6082991
48	A Molliex, J Temirov, J Lee, M Coughlin, AP Kanagaraj, HJ Kim, T Mittag, JP Taylor (2015) Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization. Cell 163: 123- 133 https://doi.org/10.1016/j.cell.2015.09.015
49	A Monette, M Niu, L Chen, S Rao, RJ Gorelick, AJ Mouland (2020) Pan-retroviral nucleocapsid-mediated phase separation regulates genomic RNA positioning and trafficking. Cell Rep 31: 107520 https://doi.org/10.1016/j.celrep.2020.03.084
50	MM Moosa, PR Banerjee (2020) Subversion of host stress granules by coronaviruses: potential roles of pi-rich disordered domains of viral nucleocapsids. J Med Virol. https://doi.org/10.1002/jmv.26195
51	K Onomoto, M Jogi, JS Yoo, R Narita, S Morimoto, A Takemura, S Sambhara, A Kawaguchi, S Osari, K Nagata et al (2012) Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PLoS ONE 7: e43031 https://doi.org/10.1371/journal.pone.0043031
52	A Paniz-Mondolfi, C Bryce, Z Grimes, RE Gordon, J Reidy, J Lednicky, EM Sordillo, M Fowkes (2020) Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol 92: 699- 702 https://doi.org/10.1002/jmv.25915
53	A Patel, HO Lee, L Jawerth, S Maharana, M Jahnel, MY Hein, S Stoynov, J Mahamid, S Saha, TM Franzmann et al (2015) A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162: 1066- 1077 https://doi.org/10.1016/j.cell.2015.07.047
54	TY Peng, KR Lee, WY Tarn (2008) Phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization. FEBS J 275: 4152- 4163 https://doi.org/10.1111/j.1742-4658.2008.06564.x
55	TM Perdikari, AC Murthy, VH Ryan, S Watters, MT Naik, NL Fawzi (2020) SARS-CoV-2 nucleocapsid protein phase-separates with RNA and with human hnRNPs. EMBO J 39: e106478
56	DSW Protter, R Parker (2016) Principles and properties of stress granules. Trends Cell Biol 26: 668- 679 https://doi.org/10.1016/j.tcb.2016.05.004
57	S Qamar, G Wang, SJ Randle, FS Ruggeri, JA Varela, JQ Lin, EC Phillips, A Miyashita, D Williams, F Strohl et al (2018) FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-pi interactions. Cell 173: 720- 734 https://doi.org/10.1016/j.cell.2018.03.056
58	B Readhead, JV Haure-Mirande, CC Funk, MA Richards, P Shannon, V Haroutunian, M Sano, WS Liang, ND Beckmann, ND Price et al (2018) Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron 99: 64- 82 https://doi.org/10.1016/j.neuron.2018.05.023
59	KS Saikatendu, JS Joseph, V Subramanian, BW Neuman, MJ Buchmeier, RC Stevens, P Kuhn (2007) Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus through molecular action of the N-terminal domain of N protein. J Virol 81: 3913- 3921 https://doi.org/10.1128/JVI.02236-06
60	A Savastano, de Opakua A Ibanez, M Rankovic, M Zweckstetter (2020) Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates. Nat Commun 11: 6041 https://doi.org/10.1038/s41467-020-19843-1
61	PJ Serrano-Castro, G Estivill-Torrus, P Cabezudo-Garcia, JA Reyes-Bueno, N Ciano Petersen, MJ Aguilar-Castillo, J Suarez-Perez, MD Jimenez-Hernandez, MA Moya-Molina, B Oliver-Martos et al (2020) Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? Neurologia 35: 245- 251 https://doi.org/10.1016/j.nrl.2020.04.002
62	CMS Singal, P Jaiswal, P Seth (2020) SARS-CoV-2, more than a respiratory virus: its potential role in neuropathogenesis. ACS Chem Neurosci 11: 1887- 1899 https://doi.org/10.1021/acschemneuro.0c00251
63	E Song, C Zhang, B Israelow, A Lu-Culligan, AV Prado, S Skriabine, P Lu, OE Weizman, F Liu, Y Dai et al (2021) Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med 218: e20202135 https://doi.org/10.1084/jem.20202135
64	A Soresina, D Moratto, M Chiarini, C Paolillo, G Baresi, E Foca, M Bezzi, B Baronio, M Giacomelli, R Badolato (2020) Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover. Pediatr Allergy Immunol 31 (5): 565- 569 https://doi.org/10.1111/pai.13263
65	I Thevarajan, THO Nguyen, M Koutsakos, J Druce, L Caly, CE van de Sandt, X Jia, S Nicholson, M Catton, B Cowie et al (2020) Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 26: 453- 455 https://doi.org/10.1038/s41591-020-0819-2
66	B Wolozin, P Ivanov (2019) Stress granules and neurodegeneration. Nat Rev Neurosci 20: 649- 666 https://doi.org/10.1038/s41583-019-0222-5
67	F Wu, S Zhao, B Yu, YM Chen, W Wang, ZG Song, Y Hu, ZW Tao, JH Tian, YY Pei et al (2020) A new coronavirus associated with human respiratory disease in China. Nature 579: 265- 269 https://doi.org/10.1038/s41586-020-2008-3
68	X Zhang, F Wang, Y Hu, R Chen, D Meng, L Guo, H Lv, J Guan, Y Jia (2020) In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model. Brain 143: 1350- 1367 https://doi.org/10.1093/brain/awaa076
69	D Zhao, W Xu, X Zhang, X Wang, Y Ge, E Yuan, Y Xiong, S Wu, S Li, N Wu et al (2021) Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2. Protein Cell 12: 734- 740 https://doi.org/10.1007/s13238-021-00832-z
70	P Zhou, XL Yang, XG Wang, B Hu, L Zhang, W Zhang, HR Si, Y Zhu, B Li, CL Huang et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270- 273 https://doi.org/10.1038/s41586-020-2012-7
71	N Zhu, D Zhang, W Wang, X Li, B Yang, J Song, X Zhao, B Huang, W Shi, R Lu et al (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382: 727- 733 https://doi.org/10.1056/NEJMoa2001017

[1]

PAC-0602-21592-LYC_suppl_1

Download

[1]	Zezhong Liu, Wei Xu, Zhenguo Chen, Wangjun Fu, Wuqiang Zhan, Yidan Gao, Jie Zhou, Yunjiao Zhou, Jianbo Wu, Qian Wang, Xiang Zhang, Aihua Hao, Wei Wu, Qianqian Zhang, Yaming Li, Kaiyue Fan, Ruihong Chen, Qiaochu Jiang, Christian T. Mayer, Till Schoofs, Youhua Xie, Shibo Jiang, Yumei Wen, Zhenghong Yuan, Kang Wang, Lu Lu, Lei Sun, Qiao Wang. An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope[J]. Protein Cell, 2022, 13(9): 655-675.
[2]	Wan Zhao, Junjie Zhu, Hong Lu, Jiaming Zhu, Fei Jiang, Wei Wang, Lan Luo, Le Kang, Feng Cui. The nucleocapsid protein of rice stripe virus in cell nuclei of vector insect regulates viral replication[J]. Protein Cell, 2022, 13(5): 360-378.
[3]	Rongjuan Pei, Jianqi Feng, Yecheng Zhang, Hao Sun, Lian Li, Xuejie Yang, Jiangping He, Shuqi Xiao, Jin Xiong, Ying Lin, Kun Wen, Hongwei Zhou, Jiekai Chen, Zhili Rong, Xinwen Chen. Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection[J]. Protein Cell, 2021, 12(9): 717-733.
[4]	Yao Zhao, Xiaoyu Du, Yinkai Duan, Xiaoyan Pan, Yifang Sun, Tian You, Lin Han, Zhenming Jin, Weijuan Shang, Jing Yu, Hangtian Guo, Qianying Liu, Yan Wu, Chao Peng, Jun Wang, Chenghao Zhu, Xiuna Yang, Kailin Yang, Ying Lei, Luke W. Guddat, Wenqing Xu, Gengfu Xiao, Lei Sun, Leike Zhang, Zihe Rao, Haitao Yang. High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors[J]. Protein Cell, 2021, 12(11): 877-888.
[5]	Hua Qin, Andong Zhao. Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics[J]. Protein Cell, 2020, 11(10): 707-722.
[6]	Rui Xiong, Leike Zhang, Shiliang Li, Yuan Sun, Minyi Ding, Yong Wang, Yongliang Zhao, Yan Wu, Weijuan Shang, Xiaming Jiang, Jiwei Shan, Zihao Shen, Yi Tong, Liuxin Xu, Yu Chen, Yingle Liu, Gang Zou, Dimitri Lavillete, Zhenjiang Zhao, Rui Wang, Lili Zhu, Gengfu Xiao, Ke Lan, Honglin Li, Ke Xu. Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2[J]. Protein Cell, 2020, 11(10): 723-739.
[7]	Yuna Sun, Yu Guo, Zhiyong Lou. A versatile building block: the structures and functions of negative-sense single-stranded RNA virus nucleocapsid proteins[J]. Prot Cell, 2012, 3(12): 893-902.
[8]	Yinyan Sun, Peiguo Yang, Yuxia Zhang, Xin Bao, Jun Li, Wenru Hou, Xiangyu Yao, Jinghua Han, Hong Zhang. A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi[J]. Prot Cell, 2011, 2(11): 918-939.
[9]	Yanlin Ma, Xiaohang Tong, Xiaoling Xu, Zhiyong Lou, Xuemei Li, Zihe Rao, . Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus[J]. Protein Cell, 2010, 1(7): 688-697.

Viewed

Full text

Abstract

Cited

Shared

Discussed