Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response.
Drugs
Immune response
Virology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
15 Sep 2023
15 Sep 2023
Historique:
received:
25
06
2023
revised:
05
07
2023
accepted:
11
08
2023
medline:
4
9
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally, screening a library of FDA-approved drugs identified indomethacin as the most potent potentiator of interferon response through increasing STAT1 phosphorylation. Combining indomethacin with interferon-alpha exerted synergistic antiviral effects against multiple coronaviruses. The anti-coronavirus activity of indomethacin is associated with activating interferon response. In a co-culture system of lung epithelial cells with macrophages, indomethacin inhibited both viral replication and inflammatory response. Collectively, indomethacin is a pan-coronavirus inhibitor that can simultaneously inhibit virus-triggered inflammatory response. The therapeutic potential of indomethacin can be further augmented by combining it with oral antiviral drugs or interferon-alpha.
Identifiants
pubmed: 37664584
doi: 10.1016/j.isci.2023.107631
pii: S2589-0042(23)01708-X
pmc: PMC10474465
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107631Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors disclose no conflicts.
Références
Nature. 2020 Nov;587(7835):619-625
pubmed: 33208946
J Virol. 2004 Dec;78(23):12964-74
pubmed: 15542648
Hepatology. 2011 Apr;53(4):1400-1; author reply 1402
pubmed: 21480347
J Infect Dis. 2020 Jul 23;222(4):695-696
pubmed: 32497175
iScience. 2022 Mar 17;25(4):104112
pubmed: 35402870
J Clin Virol. 2020 Jun;127:104370
pubmed: 32344321
Clin Microbiol Infect. 2022 Sep;28(9):1293-1296
pubmed: 35533972
Lancet Infect Dis. 2020 Sep;20(9):e238-e244
pubmed: 32628905
Antiviral Res. 2023 Mar;211:105555
pubmed: 36791846
Science. 2012 Jun 15;336(6087):1386-7
pubmed: 22700906
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Trends Immunol. 2017 Jan;38(1):1-2
pubmed: 27916385
Int J Infect Dis. 2020 Apr;93:268-276
pubmed: 32081774
Int J Mol Sci. 2021 Jan 07;22(2):
pubmed: 33430309
Comput Biol Med. 2022 Aug;147:105788
pubmed: 35809412
Viruses. 2021 Dec 11;13(12):
pubmed: 34960758
Sci Adv. 2022 Sep 16;8(37):eabo5400
pubmed: 36103544
Arch Pharm (Weinheim). 2021 Apr;354(4):e2000328
pubmed: 33314237
Trends Microbiol. 2017 Jul;25(7):573-584
pubmed: 28139375
J Med Virol. 2021 Feb;93(2):1002-1007
pubmed: 32720706
Ann Rheum Dis. 1970 Jul;29(4):393-6
pubmed: 4916769
Lancet Respir Med. 2021 Dec;9(12):1365-1376
pubmed: 34672949
Lancet Microbe. 2022 May;3(5):e325-e326
pubmed: 35309711
Antivir Ther. 2006;11(8):1021-30
pubmed: 17302372
Cell Res. 2022 Mar;32(3):322-324
pubmed: 35058606
Eur J Med Chem. 2021 Dec 15;226:113814
pubmed: 34534839
N Engl J Med. 2020 Dec 3;383(23):2255-2273
pubmed: 33264547
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7988-93
pubmed: 15897467
Am J Gastroenterol. 2005 Apr;100(4):856-61
pubmed: 15784032
J Med Virol. 2021 Jan;93(1):250-256
pubmed: 32592501
Clin Infect Dis. 2023 Feb 8;76(3):e26-e33
pubmed: 36031408
Antiviral Res. 2018 Jun;154:174-182
pubmed: 29698664
Antiviral Res. 2023 Jan;209:105475
pubmed: 36423831
Cold Spring Harb Perspect Med. 2022 May 27;12(5):
pubmed: 35444005
EBioMedicine. 2022 Jul;81:104132
pubmed: 35779493
New Microbes New Infect. 2023 Jan 18;51:101085
pubmed: 36711049
Nucleic Acids Res. 2022 Jul 5;50(W1):W739-W743
pubmed: 35580060
Front Immunol. 2023 Jan 26;14:1069894
pubmed: 36776844
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6756-61
pubmed: 24753610
Crit Rev Clin Lab Sci. 2021 Aug;58(5):297-310
pubmed: 33347790
JAMA. 2022 Jun 28;327(24):2380-2382
pubmed: 35675094
Nat Protoc. 2011 Jun;6(6):925-33
pubmed: 21637207
Lancet. 2022 Oct 8;400(10359):1213-1222
pubmed: 36216007
Sci Rep. 2022 Apr 19;12(1):6413
pubmed: 35440611
J Pharmacokinet Pharmacodyn. 2020 Jun;47(3):189-198
pubmed: 32435882
J Virol. 2021 Jan 13;95(7):
pubmed: 33441348
Br Med J. 1963 Oct 19;2(5363):965-70
pubmed: 14056924
J Virol. 2013 May;87(9):5300-4
pubmed: 23449793
Viruses. 2021 Sep 04;13(9):
pubmed: 34578348
Int J Mol Sci. 2023 Apr 07;24(8):
pubmed: 37108051
Viruses. 2021 Mar 26;13(4):
pubmed: 33810356
Hepatol Commun. 2023 Apr 4;7(4):
pubmed: 37026734
Science. 2020 Dec 4;370(6521):
pubmed: 33060197