SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis.

3a protein COVID-19 ORF3a SARS-CoV-2 nonsynonymous mutations

Journal

mSystems
ISSN: 2379-5077
Titre abrégé: mSystems
Pays: United States
ID NLM: 101680636

Informations de publication

Date de publication:
05 May 2020
Historique:
entrez: 7 5 2020
pubmed: 7 5 2020
medline: 7 5 2020
Statut: epublish

Résumé

The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation.

Identifiants

pubmed: 32371472
pii: 5/3/e00266-20
doi: 10.1128/mSystems.00266-20
pmc: PMC7205519
pii:
doi:

Types de publication

Journal Article

Langues

eng

Informations de copyright

Copyright © 2020 Issa et al.

Références

Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
Bioinformatics. 2015 Aug 15;31(16):2745-7
pubmed: 25851949
Viruses. 2020 Feb 22;12(2):
pubmed: 32098422
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Virus Res. 2008 Apr;133(1):113-21
pubmed: 18045721
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Nucleic Acids Res. 2017 Jan 4;45(D1):D313-D319
pubmed: 27899672
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W429-32
pubmed: 17483518
Bioinformatics. 2014 Mar 15;30(6):884-6
pubmed: 24162465
Bioinformatics. 2014 Jul 15;30(14):2068-9
pubmed: 24642063
Mol Biol Evol. 2015 Oct;32(10):2798-800
pubmed: 26130081
BMC Evol Biol. 2010 Jul 13;10:210
pubmed: 20626897
Viruses. 2020 Jan 24;12(2):
pubmed: 31991541
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12540-5
pubmed: 16894145
Nature. 2020 Mar 26;:
pubmed: 32218527
Int J Biochem Cell Biol. 2009 Nov;41(11):2232-9
pubmed: 19398035
Virol J. 2014 Apr 24;11:75
pubmed: 24762043
J Gen Virol. 2007 Nov;88(Pt 11):3067-77
pubmed: 17947532
J Mol Biol. 2004 Jul 30;341(1):271-9
pubmed: 15312778
FASEB J. 2019 Aug;33(8):8865-8877
pubmed: 31034780
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W362-5
pubmed: 16845026

Auteurs

Elio Issa (E)

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.

Georgi Merhi (G)

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.

Balig Panossian (B)

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.

Tamara Salloum (T)

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon.

Sima Tokajian (S)

Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Byblos, Lebanon stokajian@lau.edu.lb.

Classifications MeSH