SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.
COVID-19
/ enzymology
Coronavirus Nucleocapsid Proteins
/ genetics
Genome, Viral
Glycogen Synthase Kinase 3
/ genetics
Host-Pathogen Interactions
Humans
Mutation, Missense
Nucleocapsid
/ genetics
Phosphorylation
Phylogeny
Protein Binding
SARS-CoV-2
/ classification
Saudi Arabia
Viral Load
Virus Replication
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
10
05
2021
accepted:
12
01
2022
entrez:
2
2
2022
pubmed:
3
2
2022
medline:
12
2
2022
Statut:
epublish
Résumé
Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.
Identifiants
pubmed: 35105893
doi: 10.1038/s41467-022-28287-8
pii: 10.1038/s41467-022-28287-8
pmc: PMC8807822
doi:
Substances chimiques
Coronavirus Nucleocapsid Proteins
0
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
601Subventions
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : King Abdullah University of Science and Technology (KAUST)
ID : Rapid Research Response Team (R3T) by Vice President - Research (VPR) office in KAUST.
Organisme : Medical Research Council
ID : MC_PC_19012
Pays : United Kingdom
Organisme : King Abdullah University of Science and Technology (KAUST)
ID : KAUST faculty baseline fund (BAS/1/1020-01-01)
Organisme : King Abdulaziz City for Science and Technology (KACST)
ID : Proposal number: 5-20-01-002-0008
Informations de copyright
© 2022. The Author(s).
Références
Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
pubmed: 12824425
Virus Evol. 2018 Jan 08;4(1):vex042
pubmed: 29340210
Cell Host Microbe. 2014 Oct 8;16(4):462-72
pubmed: 25299332
Nat Commun. 2020 Oct 30;11(1):5493
pubmed: 33127906
Lancet Infect Dis. 2020 May;20(5):533-534
pubmed: 32087114
PLoS One. 2021 Sep 27;16(9):e0249254
pubmed: 34570776
Sci Data. 2019 Nov 22;6(1):278
pubmed: 31757973
Nat Microbiol. 2020 Nov;5(11):1403-1407
pubmed: 32669681
Viruses. 2020 Apr 13;12(4):
pubmed: 32294919
Lancet Microbe. 2020 Jul;1(3):e99-e100
pubmed: 32835336
Nat Commun. 2021 Jan 21;12(1):502
pubmed: 33479198
Clin Infect Dis. 2020 Jul 28;71(15):884-887
pubmed: 32130405
Ann Intern Med. 2020 May 19;172(10):699-701
pubmed: 32176272
Epigenetics Chromatin. 2019 Dec 19;12(1):78
pubmed: 31856907
iScience. 2021 Jun 25;24(6):102681
pubmed: 34095780
J Biol Chem. 2009 Feb 20;284(8):5229-39
pubmed: 19106108
J Virol. 2010 Nov;84(21):11575-9
pubmed: 20739524
J Mol Evol. 1985;22(2):160-74
pubmed: 3934395
Cell. 2021 Jan 7;184(1):64-75.e11
pubmed: 33275900
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Lancet Respir Med. 2020 Sep;8(9):e70
pubmed: 32771081
PLoS Genet. 2020 Nov 18;16(11):e1009175
pubmed: 33206635
Viruses. 2014 Aug 07;6(8):2991-3018
pubmed: 25105276
Biochem Biophys Res Commun. 2004 Apr 2;316(2):476-83
pubmed: 15020242
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Cell Host Microbe. 2021 Mar 10;29(3):489-502.e8
pubmed: 33548198
Lancet. 2020 Mar 14;395(10227):e48
pubmed: 32113506
Elife. 2019 Jan 11;8:
pubmed: 30632963
Cell. 2020 Aug 20;182(4):812-827.e19
pubmed: 32697968
Lancet Infect Dis. 2021 Jan;21(1):26-27
pubmed: 32442522
Bioinformatics. 2019 Feb 1;35(3):526-528
pubmed: 30016406
PLoS One. 2013 May 23;8(5):e65045
pubmed: 23717688
J Virol. 2005 Jan;79(2):1164-79
pubmed: 15613344
Nat Commun. 2020 Nov 27;11(1):6041
pubmed: 33247108
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Nature. 2018 Jul;559(7715):637-641
pubmed: 30022161
Mol Biol Evol. 2021 May 4;38(5):1777-1791
pubmed: 33316067
Antiviral Res. 2014 Mar;103:39-50
pubmed: 24418573
Mol Cell. 2020 Dec 17;80(6):1092-1103.e4
pubmed: 33248025
Cell Commun Signal. 2017 Jul 14;15(1):27
pubmed: 28705221
J Med Virol. 2021 Apr;93(4):2177-2195
pubmed: 33095454
Nucleic Acids Res. 2020 Jan 8;48(D1):D682-D688
pubmed: 31691826
Bioinformatics. 2018 Dec 1;34(23):4121-4123
pubmed: 29790939
Comput Struct Biotechnol J. 2020 Dec 17;19:153-160
pubmed: 33425248
Cell. 2020 Aug 6;182(3):685-712.e19
pubmed: 32645325
Euro Surveill. 2017 Mar 30;22(13):
pubmed: 28382917
Sci China Life Sci. 2020 May;63(5):706-711
pubmed: 32146694
Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15193-15199
pubmed: 32522874
Virus Evol. 2020 Aug 19;6(2):veaa061
pubmed: 33235813
Bioinformatics. 2011 Nov 1;27(21):2987-93
pubmed: 21903627
J Med Virol. 2021 Apr;93(4):2132-2140
pubmed: 33090512
Int J Infect Dis. 2020 Nov;100:216-223
pubmed: 32841689
Intensive Care Med Exp. 2020 Dec 11;8(1):75
pubmed: 33306162
PLoS Biol. 2020 Sep 8;18(9):e3000849
pubmed: 32898168
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Nature. 2021 May;593(7858):270-274
pubmed: 33723411
J Proteome Res. 2020 Jan 3;19(1):204-211
pubmed: 31657565
Database (Oxford). 2016 Jun 23;2016:
pubmed: 27337980
Nat Commun. 2020 Oct 8;11(1):5086
pubmed: 33033248
Mol Biol Evol. 2018 Feb 1;35(2):518-522
pubmed: 29077904
Mol Biol Evol. 2015 Jan;32(1):268-74
pubmed: 25371430
Nat Commun. 2022 Feb 1;13(1):601
pubmed: 35105893
Adv Exp Med Biol. 2019;1203:83-112
pubmed: 31811631
FEBS J. 2008 Aug;275(16):4152-63
pubmed: 18631359
Mol Biol Evol. 1993 May;10(3):512-26
pubmed: 8336541
Glob Chall. 2017 Jan 10;1(1):33-46
pubmed: 31565258
Bioinformatics. 2011 Feb 15;27(4):592-3
pubmed: 21169378
Nucleic Acids Res. 2019 Jul 2;47(W1):W234-W241
pubmed: 30931480
Biochem Biophys Res Commun. 2020 Jun 30;527(3):618-623
pubmed: 32416961
Syst Biol. 2018 Jul 1;67(4):719-728
pubmed: 29432602
Viruses. 2021 Feb 28;13(3):
pubmed: 33671076
Bioinformatics. 2018 Sep 15;34(18):3094-3100
pubmed: 29750242
Nature. 2020 Jul;583(7816):459-468
pubmed: 32353859
Cell. 2020 May 28;181(5):997-1003.e9
pubmed: 32359424