Comparison of anti-SARS-CoV-2 activity and intracellular metabolism of remdesivir and its parent nucleoside.

ACE2, angiotensin-converting enzyme 2 Anti-SARS-CoV-2 Antiviral agents CES1, carboxylesterase 1 COVID-19 COVID-19, coronavirus disease 2019 CatA, cathepsin A Coronavirus DP, diphosphate GS-441524 HAE, human airway epithelial HCoV-OC43 HINT1, histidine triad nucleotide-binding protein 1 MP, monophosphate NTP, nucleoside triphosphate Pharmacology Remdesivir SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 TP, triphosphate WHO, World Health Organization icSARS-CoV-2-mNG, SARS-CoV-2 infectious clone virus containing mNeonGreen reporter

Journal

Current research in pharmacology and drug discovery
ISSN: 2590-2571
Titre abrégé: Curr Res Pharmacol Drug Discov
Pays: Netherlands
ID NLM: 9918300982506676

Informations de publication

Date de publication:
2021
Historique:
received: 30 06 2021
revised: 05 08 2021
accepted: 08 08 2021
entrez: 6 12 2021
pubmed: 7 12 2021
medline: 7 12 2021
Statut: ppublish

Résumé

Remdesivir, a monophosphate prodrug of nucleoside analog GS-441524, is widely used for the treatment of moderate to severe COVID-19. It has been suggested to use GS-441524 instead of remdesivir in the clinic and in new inhalation formulations. Thus, we compared the anti-SARS-CoV-2 activity of remdesivir and GS-441524 in Vero E6, Vero CCL-81, Calu-3, Caco-2 ​cells, and anti-HCoV-OC43 activity in Huh-7 ​cells. We also compared the cellular pharmacology of these two compounds in Vero E6, Vero CCL-81, Calu-3, Caco-2, Huh-7, 293T, BHK-21, 3T3 and human airway epithelial (HAE) cells. Overall, remdesivir exhibited greater potency and superior intracellular metabolism than GS-441524 except in Vero E6 and Vero CCL-81 ​cells.

Identifiants

pubmed: 34870151
doi: 10.1016/j.crphar.2021.100045
pii: S2590-2571(21)00032-8
pmc: PMC8357487
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100045

Subventions

Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI121315
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141327
Pays : United States

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Références

Antimicrob Agents Chemother. 2020 Jun 23;64(7):
pubmed: 32366720
J Hepatol. 2020 Oct;73(4):807-816
pubmed: 32437830
Int J Infect Dis. 2020 Aug;97:7-10
pubmed: 32479865
ACS Cent Sci. 2020 May 27;6(5):672-683
pubmed: 32483554
Cell Rep Med. 2020 Jul 21;1(4):100059
pubmed: 32835306
J Med Virol. 2021 Mar;93(3):1403-1408
pubmed: 32767684
Curr Drug Metab. 2016;17(3):237-52
pubmed: 26651972
Acta Biomed. 2020 Mar 19;91(1):157-160
pubmed: 32191675
J Clin Immunol. 2021 Feb;41(2):335-344
pubmed: 33245474
Antiviral Res. 2017 Oct;146:161-163
pubmed: 28912011
Int J Mol Med. 2020 Aug;46(2):467-488
pubmed: 32468014
Nat Commun. 2020 Sep 4;11(1):4417
pubmed: 32887884
BMJ. 2020 Oct 19;371:m4057
pubmed: 33077424
Cell Res. 2020 Mar;30(3):269-271
pubmed: 32020029
Sci Transl Med. 2020 Apr 29;12(541):
pubmed: 32253226
Antiviral Res. 2021 Aug;192:105122
pubmed: 34186107
J Med Chem. 2021 Feb 1;:
pubmed: 33523654
Sci Data. 2021 Feb 26;8(1):70
pubmed: 33637768
Nucleosides Nucleotides Nucleic Acids. 2020;39(1-3):204-224
pubmed: 31595843
Clin Transl Sci. 2020 Sep;13(5):896-906
pubmed: 32589775
Cell Host Microbe. 2020 May 13;27(5):841-848.e3
pubmed: 32289263
Tissue Cell. 2021 Jun;70:101497
pubmed: 33550034
Antimicrob Agents Chemother. 2020 Dec 16;65(1):
pubmed: 33122172
Cell Rep. 2021 May 4;35(5):109055
pubmed: 33905739
J Hepatol. 2021 Jan;74(1):168-184
pubmed: 33038433
Nature. 2016 Mar 17;531(7594):381-5
pubmed: 26934220
Crit Rev Clin Lab Sci. 2020 Sep;57(6):365-388
pubmed: 32645276
Pharmaceutics. 2020 Oct 22;12(11):
pubmed: 33105618
J Virol. 1968 Oct;2(10):955-61
pubmed: 4302013
Nat Commun. 2021 Jan 28;12(1):668
pubmed: 33510133
Cell Mol Gastroenterol Hepatol. 2021;11(4):935-948
pubmed: 33186749
Nature. 2020 Sep;585(7826):588-590
pubmed: 32698190
Cell Rep. 2020 Jul 21;32(3):107940
pubmed: 32668216
N Engl J Med. 2020 Nov 5;383(19):1813-1826
pubmed: 32445440
Antimicrob Agents Chemother. 2016 Aug 22;60(9):5492-503
pubmed: 27381385
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
ACS Med Chem Lett. 2020 Jun 23;11(7):1361-1366
pubmed: 32665809
Clin Gastroenterol Hepatol. 2020 Jul;18(8):1663-1672
pubmed: 32278065
Hepatol Int. 2020 Sep;14(5):881-883
pubmed: 32725454
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0060221
pubmed: 34125594

Auteurs

Sijia Tao (S)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Keivan Zandi (K)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Leda Bassit (L)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Yee Tsuey Ong (YT)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Kiran Verma (K)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Peng Liu (P)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Jessica A Downs-Bowen (JA)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Tamara McBrayer (T)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Julia C LeCher (JC)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

James J Kohler (JJ)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Philip R Tedbury (PR)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Baek Kim (B)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Franck Amblard (F)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Stefan G Sarafianos (SG)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Raymond F Schinazi (RF)

Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Classifications MeSH