Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
03 08 2022
03 08 2022
Historique:
pubmed:
29
4
2022
medline:
6
8
2022
entrez:
28
4
2022
Statut:
ppublish
Résumé
The nucleoside analog remdesivir (RDV) is a Food and Drug Administration-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in half-maximal effective concentration from 2.7- to 10.4-fold. Sequence analysis identified nonsynonymous mutations in nonstructural protein 12 RNA-dependent RNA polymerase (
Identifiants
pubmed: 35482820
doi: 10.1126/scitranslmed.abo0718
pmc: PMC9097878
doi:
Substances chimiques
Antiviral Agents
0
RNA, Viral
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabo0718Subventions
Organisme : CIHR
ID : 170343
Pays : Canada
Références
J Virol. 2019 Nov 26;93(24):
pubmed: 31578288
J Med Chem. 2021 Apr 22;64(8):5001-5017
pubmed: 33835812
N Engl J Med. 2022 Jan 27;386(4):305-315
pubmed: 34937145
Sci Transl Med. 2020 Apr 29;12(541):
pubmed: 32253226
PLoS Pathog. 2013 Aug;9(8):e1003565
pubmed: 23966862
Cell Rep. 2020 Jul 21;32(3):107940
pubmed: 32668216
Bioinformatics. 2018 Sep 15;34(18):3094-3100
pubmed: 29750242
Cell. 2020 Sep 17;182(6):1560-1573.e13
pubmed: 32783916
PLoS Pathog. 2021 Sep 17;17(9):e1009929
pubmed: 34534263
J Infect Dis. 2021 Jul 15;224(Supplement_1):S1-S21
pubmed: 34111271
Nat Biotechnol. 2004 Dec;22(12):1583-7
pubmed: 15568020
JAMA. 2020 Sep 15;324(11):1048-1057
pubmed: 32821939
J Biol Chem. 2008 Mar 21;283(12):7705-12
pubmed: 18184655
Antimicrob Agents Chemother. 1993 Apr;37(4):875-81
pubmed: 7684216
iScience. 2020 Dec 18;23(12):101849
pubmed: 33283177
Antimicrob Agents Chemother. 2003 Jul;47(7):2376-9
pubmed: 12821504
Clin Infect Dis. 2021 Oct 5;73(7):e1762-e1765
pubmed: 32986807
J Virol. 2002 Nov;76(21):11065-78
pubmed: 12368349
Structure. 2012 Sep 5;20(9):1519-27
pubmed: 22819218
J Biol Chem. 2022 Feb;298(2):101529
pubmed: 34953856
Elife. 2021 Oct 07;10:
pubmed: 34617885
Sci Transl Med. 2017 Jun 28;9(396):
pubmed: 28659436
N Engl J Med. 2020 Sep 3;383(10):994
pubmed: 32649078
Antiviral Res. 2019 Sep;169:104541
pubmed: 31233808
mBio. 2017 Nov 7;8(6):
pubmed: 29114026
Gigascience. 2021 Feb 16;10(2):
pubmed: 33590861
J Virol. 2007 Nov;81(22):12135-44
pubmed: 17804504
J Biol Chem. 2020 Nov 20;295(47):16156-16165
pubmed: 32967965
mBio. 2018 Mar 6;9(2):
pubmed: 29511076
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776
pubmed: 32054787
Mol Cell. 2021 Apr 1;81(7):1548-1552.e4
pubmed: 33631104
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22505-10
pubmed: 21148772
J Biol Chem. 2020 Apr 10;295(15):4773-4779
pubmed: 32094225
Nat Commun. 2021 Jan 12;12(1):279
pubmed: 33436624
Emerg Infect Dis. 2020 Jun;26(6):1266-1273
pubmed: 32160149
J Virol. 2001 Jul;75(14):6321-8
pubmed: 11413298
Nature. 2016 Mar 17;531(7594):381-5
pubmed: 26934220
Nat Commun. 2020 Jan 10;11(1):222
pubmed: 31924756
Cell Rep. 2021 Jul 27;36(4):109450
pubmed: 34289384
Nat Methods. 2015 Aug;12(8):733-5
pubmed: 26076426
Viruses. 2014 Oct 23;6(10):4080-94
pubmed: 25341667
Science. 2015 Feb 13;347(6223):771-5
pubmed: 25678663
Science. 2020 Dec 18;370(6523):1464-1468
pubmed: 33184236
J Transl Med. 2020 Apr 22;18(1):179
pubmed: 32321524
J Biol Chem. 2020 May 15;295(20):6785-6797
pubmed: 32284326
Curr Protoc Protein Sci. 2008 Feb;Chapter 5:Unit 5.20
pubmed: 18429060