Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin.
SARS-CoV-2
coronavirus
inflammation
ivermectin
viral infections
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
09 08 2021
09 08 2021
Historique:
revised:
22
06
2021
received:
11
02
2021
accepted:
23
06
2021
pubmed:
26
6
2021
medline:
18
8
2021
entrez:
25
6
2021
Statut:
ppublish
Résumé
The devastating pandemic due to SARS-CoV-2 and the emergence of antigenic variants that jeopardize the efficacy of current vaccines create an urgent need for a comprehensive understanding of the pathophysiology of COVID-19, including the contribution of inflammation to disease. It also warrants for the search of immunomodulatory drugs that could improve disease outcome. Here, we show that standard doses of ivermectin (IVM), an anti-parasitic drug with potential immunomodulatory activities through the cholinergic anti-inflammatory pathway, prevent clinical deterioration, reduce olfactory deficit, and limit the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters. Whereas it has no effect on viral load in the airways of infected animals, transcriptomic analyses of infected lungs reveal that IVM dampens type I interferon responses and modulates several other inflammatory pathways. In particular, IVM dramatically reduces the Il-6/Il-10 ratio in lung tissue and promotes macrophage M2 polarization, which might account for the more favorable clinical presentation of IVM-treated animals. Altogether, this study supports the use of immunomodulatory drugs such as IVM, to improve the clinical condition of SARS-CoV-2-infected patients.
Identifiants
pubmed: 34170074
doi: 10.15252/emmm.202114122
pmc: PMC8350903
doi:
Substances chimiques
Ivermectin
70288-86-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14122Subventions
Organisme : Institut Pasteur
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
Références
PLoS One. 2016 Jun 09;11(6):e0157022
pubmed: 27280887
Bioinformatics. 2012 Oct 1;28(19):2520-2
pubmed: 22908215
Br J Dermatol. 2021 Jun;184(6):1207-1209
pubmed: 33454964
Semin Immunopathol. 2019 Mar;41(2):189-194
pubmed: 30298431
Otolaryngol Head Neck Surg. 2020 Oct;163(4):714-721
pubmed: 32539586
Mol Cells. 2020 Sep 30;43(9):774-783
pubmed: 32807748
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Biol Proced Online. 2021 Jan 20;23(1):4
pubmed: 33472576
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
J Clin Pharmacol. 2002 Oct;42(10):1122-33
pubmed: 12362927
Neuroscientist. 2021 Jun;27(3):214-221
pubmed: 32659199
Am J Physiol Lung Cell Mol Physiol. 2020 Aug 1;319(2):L277-L288
pubmed: 32551862
Bioinformatics. 2020 Jun 1;36(11):3379-3384
pubmed: 32163115
Am J Trop Med Hyg. 2020 Jun;102(6):1156-1157
pubmed: 32314704
Radiother Oncol. 2021 Jul;160:125-131
pubmed: 33932453
PLoS One. 2017 Apr 6;12(4):e0175367
pubmed: 28384302
Biosci Rep. 2018 May 8;38(3):
pubmed: 29440461
Chest. 2021 Jan;159(1):85-92
pubmed: 33065103
Front Immunol. 2020 Dec 11;11:608645
pubmed: 33362795
Bioinformatics. 2013 Dec 15;29(24):3241-2
pubmed: 24064416
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Nature. 2020 Oct;586(7830):509-515
pubmed: 32967005
J Infect. 2020 Oct;81(4):e11-e17
pubmed: 32652164
J Vis Exp. 2014 Nov 04;(93):e52065
pubmed: 25407402
Trends Parasitol. 2017 Jun;33(6):463-472
pubmed: 28285851
Elife. 2018 Apr 13;7:
pubmed: 29651984
Genome Biol. 2014;15(12):550
pubmed: 25516281
EMBO Mol Med. 2014 Aug 20;6(10):1263-78
pubmed: 25143352
Pharmacol Rep. 2021 Jun;73(3):736-749
pubmed: 33389725
Science. 2020 Oct 23;370(6515):
pubmed: 32972995
Chem Senses. 2020 Jun 17;:
pubmed: 32556089
Clin Infect Dis. 2020 Dec 3;71(9):2428-2446
pubmed: 32215622
J Clin Cell Immunol. 2015 Apr;6(2):
pubmed: 26213635
Nat Rev Neurol. 2020 Nov;16(11):645-652
pubmed: 32843733
Physiol Res. 2014;63 Suppl 1(Suppl 1):S215-24
pubmed: 24564661
Immunity. 2017 May 16;46(5):875-890.e6
pubmed: 28514692
Bioorg Chem. 2021 Jan;106:104488
pubmed: 33261844
EBioMedicine. 2020 Nov;61:103026
pubmed: 33039714
Sci Rep. 2021 Mar 30;11(1):7132
pubmed: 33785846
Brief Bioinform. 2021 Mar 22;22(2):914-923
pubmed: 32968798
EClinicalMedicine. 2021 Feb;32:100720
pubmed: 33495752
Nature. 2020 Jul;583(7818):834-838
pubmed: 32408338
Immunity. 2021 Mar 9;54(3):557-570.e5
pubmed: 33577760
Diabetes Metab Syndr Obes. 2020 Oct 21;13:3887-3898
pubmed: 33116735
Emerg Microbes Infect. 2020 Dec;9(1):1259-1268
pubmed: 32438868
Vet Rec. 2001 Sep 15;149(11):324-7
pubmed: 11583127
Science. 2020 Oct 23;370(6515):
pubmed: 32972996
EMBO Mol Med. 2021 Aug 9;13(8):e14122
pubmed: 34170074
J Antibiot (Tokyo). 2020 Sep;73(9):593-602
pubmed: 32533071
Paediatr Respir Rev. 2017 Jun;23:40-49
pubmed: 28416135
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Vet Parasitol. 2000 Feb 1;87(4):327-38
pubmed: 10669102
Parasitology. 2006 Mar;132(Pt 3):301-13
pubmed: 16332285
J Neurosci Res. 2017 Jan 2;95(1-2):422-436
pubmed: 27870426
J Hematol Oncol. 2020 Sep 4;13(1):120
pubmed: 32887634
Antiviral Res. 2020 Jun;178:104787
pubmed: 32251768
Virus Res. 2011 Sep;160(1-2):360-6
pubmed: 21816185
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
J Pharm Sci. 2020 Dec;109(12):3574-3578
pubmed: 32891630
Cell. 2020 Aug 6;182(3):734-743.e5
pubmed: 32643603
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Rev Immunol. 2020 Jul;20(7):442-447
pubmed: 32528136
Nat Rev Endocrinol. 2012 Dec;8(12):743-54
pubmed: 23169440
Nat Commun. 2020 Nov 17;11(1):5838
pubmed: 33203860
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
Front Mol Neurosci. 2009 Aug 20;2:9
pubmed: 19738917
PLoS One. 2020 Nov 11;15(11):e0242184
pubmed: 33175880
C R Biol. 2020 Jun 05;343(1):33-39
pubmed: 32720486
J Cell Physiol. 2021 Apr;236(4):2959-2975
pubmed: 32959892
Vector Borne Zoonotic Dis. 2011 Jan;11(1):43-52
pubmed: 20518644
Nucleic Acids Res. 2015 Jan;43(Database issue):D1057-63
pubmed: 25378336
Trends Pharmacol Sci. 1999 Apr;20(4):132-4
pubmed: 10322497
Diabetes. 2020 Oct;69(10):2048-2053
pubmed: 32778570
Front Immunol. 2016 Mar 31;7:123
pubmed: 27065076
Antiviral Res. 2020 Jun;178:104805
pubmed: 32330482
Nucleic Acids Res. 2019 Jan 8;47(D1):D419-D426
pubmed: 30407594
Lancet Infect Dis. 2020 Sep;20(9):1015-1016
pubmed: 32304629
Pharmacol Res. 2020 Feb;152:104602
pubmed: 31846761
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Am J Respir Crit Care Med. 2020 Sep 15;202(6):812-821
pubmed: 32584597
Am J Ther. 2021 Apr 22;28(3):e299-e318
pubmed: 34375047
Infection. 2021 Feb;49(1):117-126
pubmed: 33231841
Nature. 2011 Jun 2;474(7349):54-60
pubmed: 21572436
J Neurosci. 2012 Mar 14;32(11):3652-64
pubmed: 22423088
Front Immunol. 2020 Jul 10;11:1648
pubmed: 32754159
FEBS J. 2020 Sep;287(17):3656-3663
pubmed: 32790936
Front Public Health. 2020 Apr 29;8:152
pubmed: 32411652
Sci Transl Med. 2021 Jun 2;13(596):
pubmed: 33941622
Cell Stem Cell. 2020 Dec 3;27(6):876-889.e12
pubmed: 33232663
Eur J Pharmacol. 2020 Nov 15;887:173594
pubmed: 32971089
N Engl J Med. 2020 Apr 23;382(17):1653-1659
pubmed: 32227760
Andrology. 2021 Jan;9(1):33-38
pubmed: 32526061
Mol Pharmacol. 1998 Feb;53(2):283-94
pubmed: 9463487
Inflammation. 2019 Dec;42(6):2236-2245
pubmed: 31522340