Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model
et al., The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0, Sep 2022 (preprint)
Ivermectin for COVID-19
4th treatment shown to reduce risk in
August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
Hamster study showing that prophylactic ivermectin inhibited COVID-19 weight loss, reduced lung viral titer by a factor of 10, inhibited pulmonary inflammatory cytokine expression, and reduced the severity of pathological changes with a single 1mg/kg dose. Authors also tested 250 and 500µg/kg for inhibition of weight loss, showing a dose-response relationship. While not statistically significant, 500µg/kg also showed a trend for benefit.
74 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N771, Dengue37,72,73 , HIV-173, Simian virus 4074, Zika37,75,76 , West Nile76, Yellow Fever77,78, Japanese encephalitis77, Chikungunya78, Semliki Forest virus78, Human papillomavirus57, Epstein-Barr57, BK Polyomavirus79, and Sindbis virus78.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins71,73,74,80 , shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing38, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination41,81, shows dose-dependent inhibition of wildtype and omicron variants36, exhibits dose-dependent inhibition of lung injury61,66, may inhibit SARS-CoV-2 via IMPase inhibition37, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation9, inhibits SARS-CoV-2 3CLpro54, may inhibit SARS-CoV-2 RdRp activity28, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages60, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation82, may interfere with SARS-CoV-2's immune evasion via ORF8 binding4, may inhibit SARS-CoV-2 by disrupting CD147 interaction83-86, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1959,87, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage8, may minimize SARS-CoV-2 induced cardiac damage40,48, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation88, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses1, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways35, increases Bifidobacteria which play a key role in the immune system89, has immunomodulatory51 and anti-inflammatory70,90 properties, and has an extensive and very positive safety profile91.
1.
Gayozo et al., Binding affinities analysis of ivermectin, nucleocapsid and ORF6 proteins of SARS-CoV-2 to human importins α isoforms: A computational approach, Biotecnia, doi:10.18633/biotecnia.v27.2485.
2.
Lefebvre et al., Characterization and Fluctuations of an Ivermectin Binding Site at the Lipid Raft Interface of the N-Terminal Domain (NTD) of the Spike Protein of SARS-CoV-2 Variants, Viruses, doi:10.3390/v16121836.
3.
Haque et al., Exploring potential therapeutic candidates against COVID-19: a molecular docking study, Discover Molecules, doi:10.1007/s44345-024-00005-5.
4.
Bagheri-Far et al., Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8, Molecular Biology Research Communications, doi:10.22099/mbrc.2024.50245.2001.
5.
de Oliveira Só et al., In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease, Preprints, doi:10.20944/preprints202404.1825.v1.
6.
Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.
7.
Oranu et al., Validation of the binding affinities and stabilities of ivermectin and moxidectin against SARS-CoV-2 receptors using molecular docking and molecular dynamics simulation, GSC Biological and Pharmaceutical Sciences, doi:10.30574/gscbps.2024.26.1.0030.
8.
Zhao et al., Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis, Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752.
9.
Vottero et al., Computational Prediction of the Interaction of Ivermectin with Fibrinogen, Molecular Sciences, doi:10.3390/ijms241411449.
10.
Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors, Journal of King Saud University - Science, doi:10.1016/j.jksus.2022.102277.
11.
Umar et al., Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein and some nonstructural proteins of SARS-CoV-2: Virtual screening approach, Jurnal Teknologi Laboratorium, doi:10.29238/teknolabjournal.v11i1.344.
12.
Alvarado et al., Interaction of the New Inhibitor Paxlovid (PF-07321332) and Ivermectin With the Monomer of the Main Protease SARS-CoV-2: A Volumetric Study Based on Molecular Dynamics, Elastic Networks, Classical Thermodynamics and SPT, Computational Biology and Chemistry, doi:10.1016/j.compbiolchem.2022.107692.
13.
Aminpour et al., In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds, Computation, doi:10.3390/computation10040051.
14.
Parvez et al., Insights from a computational analysis of the SARS-CoV-2 Omicron variant: Host–pathogen interaction, pathogenicity, and possible drug therapeutics, Immunity, Inflammation and Disease, doi:10.1002/iid3.639.
15.
Francés-Monerris et al., Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection, Physical Chemistry Chemical Physics, doi:10.1039/D1CP02967C.
16.
González-Paz et al., Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach, Biophysical Chemistry, doi:10.1016/j.bpc.2021.106677.
17.
González-Paz (B) et al., Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models, Journal of Molecular Liquids, doi:10.1016/j.molliq.2021.117284.
18.
Rana et al., A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection, Research Square, doi:10.21203/rs.3.rs-755838/v1.
19.
Muthusamy et al., Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein, Journal of Virology & Antiviral Research, www.scitechnol.com/abstract/virtual-screening-reveals-potential-antiparasitic-drugs-inhibiting-the-receptor-binding-domain-of-sarscov2-spike-protein-16398.html.
20.
Qureshi et al., Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750.
21.
Schöning et al., Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains, Research Square, doi:10.21203/rs.3.rs-379291/v1.
22.
Bello et al., Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1911857.
23.
Udofia et al., In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV, Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2.
24.
Choudhury et al., Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach, Future Medicine, doi:10.2217/fvl-2020-0342.
25.
Kern et al., Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing, Frontiers in Pharmacology, doi:10.3389/fphar.2021.625678.
26.
Saha et al., The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2, Structural Chemistry, doi:10.1007/s11224-021-01776-0.
27.
Eweas et al., Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2, Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908.
28.
Parvez (B) et al., Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach, International Journal of Biological Macromolecules, doi:10.1016/j.ijbiomac.2020.09.098.
29.
Francés-Monerris (B) et al., Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent, ChemRxiv, doi:10.26434/chemrxiv.12782258.v1.
30.
Kalhor et al., Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1824816.
31.
Swargiary, A., Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies, Research Square, doi:10.21203/rs.3.rs-73308/v1.
32.
Maurya, D., A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients, American Chemical Society (ACS), doi:10.26434/chemrxiv.12630539.v1.
33.
Lehrer et al., Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2, In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134.
34.
Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, Preprints, doi:10.20944/preprints202005.0439.v3.
35.
Kofler et al., M-Motif, a potential non-conventional NLS in YAP/TAZ and other cellular and viral proteins that inhibits classic protein import, iScience, doi:10.1016/j.isci.2025.112105.
36.
Shahin et al., The selective effect of Ivermectin on different human coronaviruses; in-vitro study, Research Square, doi:10.21203/rs.3.rs-4180797/v1.
37.
Jitobaom et al., Identification of inositol monophosphatase as a broad‐spectrum antiviral target of ivermectin, Journal of Medical Virology, doi:10.1002/jmv.29552.
38.
Fauquet et al., Microfluidic Diffusion Sizing Applied to the Study of Natural Products and Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction, Molecules, doi:10.3390/molecules28248072.
39.
García-Aguilar et al., In Vitro Analysis of SARS-CoV-2 Spike Protein and Ivermectin Interaction, International Journal of Molecular Sciences, doi:10.3390/ijms242216392.
40.
Liu et al., SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to impair survival and function of human pluripotent stem cell-derived cardiomyocytes, Stem Cell Research & Therapy, doi:10.1186/s13287-023-03485-3.
41.
Boschi et al., SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects, bioRxiv, doi:10.1101/2022.11.24.517882.
42.
De Forni et al., Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients, PLoS ONE, doi:10.1371/journal.pone.0276751.
43.
Saha (B) et al., Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder, Pharmaceutics, doi:10.3390/pharmaceutics14071432.
44.
Jitobaom (B) et al., Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations, BMC Pharmacology and Toxicology, doi:10.1186/s40360-022-00580-8.
45.
Croci et al., Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin, International Journal of Biomaterials, doi:10.1155/2016/8043983.
46.
Zheng et al., Red blood cell-hitchhiking mediated pulmonary delivery of ivermectin: Effects of nanoparticle properties, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121719.
47.
Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.
48.
Liu (B) et al., Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human pluripotent stem cell-derived cardiomyocytes, Stem Cell Reports, doi:10.1016/j.stemcr.2022.01.014.
49.
Segatori et al., Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients, Viruses, doi:10.3390/v13102084.
50.
Jitobaom (C) et al., Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity against SARS-CoV-2, Research Square, doi:10.21203/rs.3.rs-941811/v1.
51.
Munson et al., Niclosamide and ivermectin modulate caspase-1 activity and proinflammatory cytokine secretion in a monocytic cell line, British Society For Nanomedicine Early Career Researcher Summer Meeting, 2021, web.archive.org/web/20230401070026/https://michealmunson.github.io/COVID.pdf.
52.
Mountain Valley MD, Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™, www.globenewswire.com/en/news-release/2021/05/18/2231755/0/en/Mountain-Valley-MD-Receives-Successful-Results-From-BSL-4-COVID-19-Clearance-Trial-on-Three-Variants-Tested-With-Ivectosol.html.
53.
Yesilbag et al., Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro, Virus Research, doi:10.1016/j.virusres.2021.198384.
54.
Mody et al., Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents, Communications Biology, doi:10.1038/s42003-020-01577-x.
55.
Jeffreys et al., Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2, International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542.
56.
Surnar et al., Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19, ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179.
57.
Li et al., Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment, J. Cellular Physiology, doi:10.1002/jcp.30055.
58.
Caly et al., The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research, doi:10.1016/j.antiviral.2020.104787.
59.
Zhang et al., Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflammation Research, doi:10.1007/s00011-008-8007-8.
60.
Gao et al., Ivermectin ameliorates acute myocarditis via the inhibition of importin-mediated nuclear translocation of NF-κB/p65, International Immunopharmacology, doi:10.1016/j.intimp.2024.112073.
61.
Abd-Elmawla et al., Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis, Journal of Zhejiang University-SCIENCE B, doi:10.1631/jzus.B2200385.
62.
Uematsu et al., Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model, The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0.
63.
Albariqi et al., Pharmacokinetics and Safety of Inhaled Ivermectin in Mice as a Potential COVID-19 Treatment, International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121688.
64.
Errecalde et al., Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model, Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017.
65.
Madrid et al., Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation, Heliyon, doi:10.1016/j.heliyon.2020.e05820.
66.
Ma et al., Ivermectin contributes to attenuating the severity of acute lung injury in mice, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113706.
67.
de Melo et al., Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin, EMBO Mol. Med., doi:10.15252/emmm.202114122.
68.
Arévalo et al., Ivermectin reduces in vivo coronavirus infection in a mouse experimental model, Scientific Reports, doi:10.1038/s41598-021-86679-0.
69.
Chaccour et al., Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats, Scientific Reports, doi:10.1038/s41598-020-74084-y.
70.
Yan et al., Anti-inflammatory effects of ivermectin in mouse model of allergic asthma, Inflammation Research, doi:10.1007/s00011-011-0307-8.
71.
Götz et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Scientific Reports, doi:10.1038/srep23138.
72.
Tay et al., Nuclear localization of dengue virus (DENV) 1–4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antiviral Research, doi:10.1016/j.antiviral.2013.06.002.
73.
Wagstaff et al., Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochemical Journal, doi:10.1042/BJ20120150.
74.
Wagstaff (B) et al., An AlphaScreen®-Based Assay for High-Throughput Screening for Specific Inhibitors of Nuclear Import, SLAS Discovery, doi:10.1177/1087057110390360.
75.
Barrows et al., A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection, Cell Host & Microbe, doi:10.1016/j.chom.2016.07.004.
76.
Yang et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral Research, doi:10.1016/j.antiviral.2020.104760.
77.
Mastrangelo et al., Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dks147.
78.
Varghese et al., Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses, Antiviral Research, doi:10.1016/j.antiviral.2015.12.012.
79.
Bennett et al., Role of a nuclear localization signal on the minor capsid Proteins VP2 and VP3 in BKPyV nuclear entry, Virology, doi:10.1016/j.virol.2014.10.013.
80.
Kosyna et al., The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biological Chemistry, doi:10.1515/hsz-2015-0171.
81.
Scheim et al., Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19, International Journal of Molecular Sciences, doi:10.3390/ijms242317039.
82.
Liu (C) et al., Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury, Frontiers in Immunology, doi:10.3389/fimmu.2023.1324021.
83.
Shouman et al., SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147, Cell Communication and Signaling, doi:10.1186/s12964-024-01718-3.
84.
Scheim (B), D., Ivermectin for COVID-19 Treatment: Clinical Response at Quasi-Threshold Doses Via Hypothesized Alleviation of CD147-Mediated Vascular Occlusion, SSRN, doi:10.2139/ssrn.3636557.
85.
Scheim (C), D., From Cold to Killer: How SARS-CoV-2 Evolved without Hemagglutinin Esterase to Agglutinate and Then Clot Blood Cells, Center for Open Science, doi:10.31219/osf.io/sgdj2.
86.
Behl et al., CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target, Science of The Total Environment, doi:10.1016/j.scitotenv.2021.152072.
87.
DiNicolantonio et al., Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19, Open Heart, doi:10.1136/openhrt-2020-001350.
88.
Mothae et al., SARS-CoV-2 host-pathogen interactome: insights into more players during pathogenesis, Virology, doi:10.1016/j.virol.2025.110607.
89.
Hazan et al., Treatment with Ivermectin Increases the Population of Bifidobacterium in the Gut, ACG 2023, acg2023posters.eventscribe.net/posterspeakers.asp.
Uematsu et al., 15 Sep 2022, peer-reviewed, 6 authors.
Contact: tuematsu@insti.kitasato-u.ac.jp.
Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model
The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0
, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity. Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In the present study, we investigated the in vivo effects of ivermectin in a hamster model of SARS-CoV-2 infection. The results of the present study demonstrate oral administration of ivermectin prior to SARS-CoV-2 infection in hamsters was associated with decreased weight loss and pulmonary inflammation. In addition, the administration of ivermectin reduced pulmonary viral titers and mRNA expression level of pro-inflammatory cytokines associated with severe COVID-19 disease. The administration of ivermectin rapidly induced the production of virus-specific neutralizing antibodies in the late stage of viral infection. Zinc concentrations leading to immune quiescence were also significantly higher in the lungs of ivermectin-treated hamsters compared to controls. These results indicate that ivermectin may have efficacy in reducing the development and severity of COVID-19 by affecting host immunity in a hamster model of SARS-CoV-2 infection.
Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41429-023-00623-0. Infectious Diseases from the Japan Agency for Medical Research and Development, under grant JP20fk0108158 to HH.
Compliance with ethical standards Conflict of interest The authors declare no competing interests. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
References
Arévalo, Ivermectin reduces in vivo coronavirus infection in a mouse experimental model, Sci Rep
Blondeau, Immunomodulatory Effects of Macrolides Considering Evidence from Human and Veterinary Medicine, Microorganisms
Brevini, FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2, Nature
Caly, Druce, Catton, Jans, Wagstaff, The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir Res
Chan, Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility, Clin Infect Dis
Collier, Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies, Nature
Crump, Omura, Ivermectin, 'Wonder drug' from Japan: The human use perspective, Proc Jpn Acad Sers B Phys Biol Sci
De Melo, Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin, EMBO Mol Med
Ebisudani, Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening, Cell Rep
Flerlage, Boyd, Meliopoulos, Thomas, Schultz-Cherry, Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract, Nat Rev Microbiol
Hirano, Roles of Zinc and Zinc Signaling in Immunity: Zinc as an Intracellular Signaling Molecule, Adv Immunol
Imai, Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development, Proc Nat Acad Sci
Israel, Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection: test negative design study, BMJ
Jin, The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism, Nat Commun
Kaur, Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes, Pharm Rep
Khezri, Zolbanin, Ghasemnejad-Berenji, Jafari, Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection, Eur J Pharm
Kitamura, Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function, Nat Immunol
Kumar, Kubota, Chernov, Kasuya, Potential role of zinc supplementation in prophylaxis and treatment of COVID-19, Med Hypotheses
Ladds, Persistent symptoms after Covid-19: qualitative study of 114 "long Covid" patients and draft quality principles for services, BMC Health Serv Res
Matsuyama, Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells, Proc Nat Acad Sci
Nambara, Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer, Oncotarget
Namkoong, Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and postinfluenza bacterial pneumonia, PLoS Pathog
Nishio, Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice, Proc Natl Acad Sci
Popp, Ivermectin for preventing and treating COVID-19, Cochrane Database Syst Rev
Puntmann, Vo, Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered from Coronavirus Disease 2019 (COVID-19), JAMA Cardiol
Ramos-Casals, Brito-Zerón, Systemic and organspecific immune-related manifestations of COVID-19, Nat Rev Rheumatol
Rawat, Kumari, Saha, COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies, Eur J Pharm
Schultze, Aschenbrenner, COVID-19 and the human innate immune system, Cell
Sharma, Sultan, Ding, Triggle, A Review of the Progress and Challenges of Developing a Vaccine for COVID-19, Front Immunol
Sia, Pathogenesis and transmission of SARS-CoV-2 in golden hamsters, Nature
Stratton, Tang, Lu, Pathogenesis-directed therapy of 2019 novel coronavirus disease, J Med Virol
Velthuis, Zn2+ Inhibits Coronavirus and RNA Polymerase Activity In and Zinc Ionophores Block the Replication of These Viruses in Cell Culture, PLoS Pathog
Venditto, Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19, Front Immunol
Vig, Kinet, Calcium signaling in immune cells, Nat Immunol
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem J
Wang, SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease, Emerg Microbes Infect
Wiersinga, Rhodes, Cheng, Peacock, Prescott, Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review, JAMA
Xu, Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus, PLoS Negl Trop Dis
Yang, The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antivir Res
Õmura, Crump, The life and times of ivermectin-A success story, Nat Rev Microbiol
DOI record:
{
"DOI": "10.1038/s41429-023-00623-0",
"ISSN": [
"0021-8820",
"1881-1469"
],
"URL": "http://dx.doi.org/10.1038/s41429-023-00623-0",
"abstract": "<jats:title>Abstract</jats:title><jats:p>COVID-19, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by <jats:italic>Streptomyces avermitilis</jats:italic>, is a macrocyclic lactone with antiparasitic activity. Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In the present study, we investigated the in vivo effects of ivermectin in a hamster model of SARS-CoV-2 infection. The results of the present study demonstrate oral administration of ivermectin prior to SARS-CoV-2 infection in hamsters was associated with decreased weight loss and pulmonary inflammation. In addition, the administration of ivermectin reduced pulmonary viral titers and mRNA expression level of pro-inflammatory cytokines associated with severe COVID-19 disease. The administration of ivermectin rapidly induced the production of virus-specific neutralizing antibodies in the late stage of viral infection. Zinc concentrations leading to immune quiescence were also significantly higher in the lungs of ivermectin-treated hamsters compared to controls. These results indicate that ivermectin may have efficacy in reducing the development and severity of COVID-19 by affecting host immunity in a hamster model of SARS-CoV-2 infection.</jats:p>",
"alternative-id": [
"623"
],
"assertion": [
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Received",
"name": "received",
"order": 1,
"value": "5 January 2023"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Revised",
"name": "revised",
"order": 2,
"value": "22 March 2023"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Accepted",
"name": "accepted",
"order": 3,
"value": "5 April 2023"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "First Online",
"name": "first_online",
"order": 4,
"value": "25 April 2023"
},
{
"group": {
"label": "Compliance with ethical standards",
"name": "EthicsHeading"
},
"name": "Ethics",
"order": 1
},
{
"group": {
"label": "Conflict of interest",
"name": "EthicsHeading"
},
"name": "Ethics",
"order": 2,
"value": "The authors declare no competing interests."
}
],
"author": [
{
"ORCID": "http://orcid.org/0000-0002-3680-7231",
"affiliation": [],
"authenticated-orcid": false,
"family": "Uematsu",
"given": "Takayuki",
"sequence": "first"
},
{
"affiliation": [],
"family": "Takano",
"given": "Tomomi",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-0099-3340",
"affiliation": [],
"authenticated-orcid": false,
"family": "Matsui",
"given": "Hidehito",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Kobayashi",
"given": "Noritada",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ōmura",
"given": "Satoshi",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hanaki",
"given": "Hideaki",
"sequence": "additional"
}
],
"container-title": "The Journal of Antibiotics",
"container-title-short": "J Antibiot",
"content-domain": {
"crossmark-restriction": false,
"domain": [
"link.springer.com"
]
},
"created": {
"date-parts": [
[
2023,
4,
25
]
],
"date-time": "2023-04-25T10:03:30Z",
"timestamp": 1682417010000
},
"deposited": {
"date-parts": [
[
2023,
4,
25
]
],
"date-time": "2023-04-25T10:07:43Z",
"timestamp": 1682417263000
},
"indexed": {
"date-parts": [
[
2023,
4,
26
]
],
"date-time": "2023-04-26T05:01:39Z",
"timestamp": 1682485299130
},
"is-referenced-by-count": 0,
"issued": {
"date-parts": [
[
2023,
4,
25
]
]
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2023,
4,
25
]
],
"date-time": "2023-04-25T00:00:00Z",
"timestamp": 1682380800000
}
},
{
"URL": "https://creativecommons.org/licenses/by/4.0",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2023,
4,
25
]
],
"date-time": "2023-04-25T00:00:00Z",
"timestamp": 1682380800000
}
}
],
"link": [
{
"URL": "https://www.nature.com/articles/s41429-023-00623-0.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://www.nature.com/articles/s41429-023-00623-0",
"content-type": "text/html",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://www.nature.com/articles/s41429-023-00623-0.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "297",
"original-title": [],
"prefix": "10.1038",
"published": {
"date-parts": [
[
2023,
4,
25
]
]
},
"published-online": {
"date-parts": [
[
2023,
4,
25
]
]
},
"publisher": "Springer Science and Business Media LLC",
"reference": [
{
"DOI": "10.1001/jama.2020.12839",
"author": "WJ Wiersinga",
"doi-asserted-by": "publisher",
"first-page": "782",
"journal-title": "JAMA",
"key": "623_CR1",
"unstructured": "Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324:782–93.",
"volume": "324",
"year": "2020"
},
{
"DOI": "10.1038/s41584-021-00608-z",
"author": "M Ramos-Casals",
"doi-asserted-by": "publisher",
"first-page": "315",
"journal-title": "Nat Rev Rheumatol",
"key": "623_CR2",
"unstructured": "Ramos-Casals M, Brito-Zerón P, Mariette X. Systemic and organ-specific immune-related manifestations of COVID-19. Nat Rev Rheumatol. 2021;17:315–32.",
"volume": "17",
"year": "2021"
},
{
"DOI": "10.1001/jamacardio.2020.3557",
"author": "VO Puntmann",
"doi-asserted-by": "publisher",
"first-page": "1265",
"journal-title": "JAMA Cardiol",
"key": "623_CR3",
"unstructured": "Puntmann VO, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered from Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5:1265–73.",
"volume": "5",
"year": "2020"
},
{
"DOI": "10.1186/s12913-020-06001-y",
"author": "E Ladds",
"doi-asserted-by": "publisher",
"journal-title": "BMC Health Serv Res",
"key": "623_CR4",
"unstructured": "Ladds E, et al. Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services. BMC Health Serv Res. 2020;20:1144.",
"volume": "20",
"year": "2020"
},
{
"DOI": "10.3389/fimmu.2020.585354",
"author": "O Sharma",
"doi-asserted-by": "publisher",
"first-page": "585354",
"journal-title": "Front Immunol",
"key": "623_CR5",
"unstructured": "Sharma O, Sultan AA, Ding H, Triggle CR. A Review of the Progress and Challenges of Developing a Vaccine for COVID-19. Front Immunol. 2020;11:585354.",
"volume": "11",
"year": "2020"
},
{
"DOI": "10.1016/j.ejphar.2020.173751",
"author": "K Rawat",
"doi-asserted-by": "publisher",
"first-page": "173751",
"journal-title": "Eur J Pharm",
"key": "623_CR6",
"unstructured": "Rawat K, Kumari P, Saha L. COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies. Eur J Pharm. 2021;892:173751.",
"volume": "892",
"year": "2021"
},
{
"DOI": "10.1038/s41586-021-03412-7",
"author": "DA Collier",
"doi-asserted-by": "publisher",
"first-page": "136",
"journal-title": "Nature",
"key": "623_CR7",
"unstructured": "Collier DA, et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature. 2021;593:136–41.",
"volume": "593",
"year": "2021"
},
{
"DOI": "10.1136/bmj-2021-067873",
"author": "A Israel",
"doi-asserted-by": "publisher",
"first-page": "e067873",
"journal-title": "BMJ",
"key": "623_CR8",
"unstructured": "Israel A, et al. Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection: test negative design study. BMJ. 2021;375:e067873.",
"volume": "375",
"year": "2021"
},
{
"DOI": "10.1038/nrmicro1048",
"author": "S Õmura",
"doi-asserted-by": "publisher",
"first-page": "984",
"journal-title": "Nat Rev Microbiol",
"key": "623_CR9",
"unstructured": "Õmura S, Crump A. The life and times of ivermectin—A success story. Nat Rev Microbiol. 2004;2:984–9.",
"volume": "2",
"year": "2004"
},
{
"DOI": "10.2183/pjab.87.13",
"author": "A Crump",
"doi-asserted-by": "publisher",
"first-page": "13",
"journal-title": "Proc Jpn Acad Sers B Phys Biol Sci",
"key": "623_CR10",
"unstructured": "Crump A, Omura S. Ivermectin, ‘Wonder drug’ from Japan: The human use perspective. Proc Jpn Acad Sers B Phys Biol Sci. 2011;87:13–28.",
"volume": "87",
"year": "2011"
},
{
"DOI": "10.1016/j.antiviral.2020.104787",
"author": "L Caly",
"doi-asserted-by": "publisher",
"first-page": "104787",
"journal-title": "Antivir Res",
"key": "623_CR11",
"unstructured": "Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res. 2020;178:104787.",
"volume": "178",
"year": "2020"
},
{
"author": "M Popp",
"first-page": "CD015017",
"journal-title": "Cochrane Database Syst Rev",
"key": "623_CR12",
"unstructured": "Popp M, et al. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2022;6:CD015017.",
"volume": "6",
"year": "2022"
},
{
"DOI": "10.1038/s41586-020-2342-5",
"author": "SF Sia",
"doi-asserted-by": "publisher",
"first-page": "834",
"journal-title": "Nature",
"key": "623_CR13",
"unstructured": "Sia SF, et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature. 2020;583:834–8.",
"volume": "583",
"year": "2020"
},
{
"DOI": "10.1073/pnas.2009799117",
"author": "M Imai",
"doi-asserted-by": "publisher",
"first-page": "16587",
"journal-title": "Proc Nat Acad Sci USA",
"key": "623_CR14",
"unstructured": "Imai M, et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development. Proc Nat Acad Sci USA. 2020;117:16587–95.",
"volume": "117",
"year": "2020"
},
{
"DOI": "10.1093/cid/ciaa644",
"author": "JF-W Chan",
"doi-asserted-by": "publisher",
"first-page": "2428",
"journal-title": "Clin Infect Dis",
"key": "623_CR15",
"unstructured": "Chan JF-W, et al. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin Infect Dis. 2020;71:2428–46.",
"volume": "71",
"year": "2020"
},
{
"DOI": "10.1016/j.celrep.2021.109218",
"author": "T Ebisudani",
"doi-asserted-by": "publisher",
"first-page": "109218",
"journal-title": "Cell Rep",
"key": "623_CR16",
"unstructured": "Ebisudani T, et al. Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening. Cell Rep. 2021;35:109218.",
"volume": "35",
"year": "2021"
},
{
"DOI": "10.1073/pnas.2002589117",
"author": "S Matsuyama",
"doi-asserted-by": "publisher",
"first-page": "7001",
"journal-title": "Proc Nat Acad Sci USA",
"key": "623_CR17",
"unstructured": "Matsuyama S, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Nat Acad Sci USA. 2020;117:7001–3.",
"volume": "117",
"year": "2020"
},
{
"DOI": "10.1016/j.cell.2021.02.029",
"author": "JL Schultze",
"doi-asserted-by": "publisher",
"first-page": "1671",
"journal-title": "Cell",
"key": "623_CR18",
"unstructured": "Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell. 2021;184:1671–92.",
"volume": "184",
"year": "2021"
},
{
"DOI": "10.1038/s41579-021-00542-7",
"author": "T Flerlage",
"doi-asserted-by": "publisher",
"first-page": "425",
"journal-title": "Nat Rev Microbiol",
"key": "623_CR19",
"unstructured": "Flerlage T, Boyd DF, Meliopoulos V, Thomas PG, Schultz-Cherry S. Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract. Nat Rev Microbiol. 2021;19:425–41.",
"volume": "19",
"year": "2021"
},
{
"DOI": "10.1073/pnas.1517188113",
"author": "M Nishio",
"doi-asserted-by": "publisher",
"first-page": "E71",
"journal-title": "Proc Natl Acad Sci USA",
"key": "623_CR20",
"unstructured": "Nishio M, et al. Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice. Proc Natl Acad Sci USA. 2016;113:E71–80.",
"volume": "113",
"year": "2016"
},
{
"DOI": "10.18632/oncotarget.22587",
"author": "S Nambara",
"doi-asserted-by": "publisher",
"first-page": "107666",
"journal-title": "Oncotarget",
"key": "623_CR21",
"unstructured": "Nambara S, et al. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer. Oncotarget. 2017;8:107666–77.",
"volume": "8",
"year": "2017"
},
{
"DOI": "10.1042/BJ20120150",
"author": "KM Wagstaff",
"doi-asserted-by": "publisher",
"first-page": "851",
"journal-title": "Biochem J",
"key": "623_CR22",
"unstructured": "Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443:851–6.",
"volume": "443",
"year": "2012"
},
{
"DOI": "10.1371/journal.pntd.0006934",
"author": "TL Xu",
"doi-asserted-by": "publisher",
"first-page": "e0006934",
"journal-title": "PLoS Negl Trop Dis",
"key": "623_CR23",
"unstructured": "Xu TL, et al. Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus. PLoS Negl Trop Dis. 2018;12:e0006934.",
"volume": "12",
"year": "2018"
},
{
"DOI": "10.1016/j.antiviral.2020.104760",
"author": "SNY Yang",
"doi-asserted-by": "publisher",
"first-page": "104760",
"journal-title": "Antivir Res",
"key": "623_CR24",
"unstructured": "Yang SNY, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antivir Res. 2020;177:104760.",
"volume": "177",
"year": "2020"
},
{
"DOI": "10.1002/jmv.26610",
"author": "CW Stratton",
"doi-asserted-by": "publisher",
"first-page": "1320",
"journal-title": "J Med Virol",
"key": "623_CR25",
"unstructured": "Stratton CW, Tang YW, Lu H. Pathogenesis-directed therapy of 2019 novel coronavirus disease. J Med Virol. 2021;93:1320–42.",
"volume": "93",
"year": "2021"
},
{
"DOI": "10.1080/22221751.2020.1823890",
"author": "P Wang",
"doi-asserted-by": "publisher",
"first-page": "2091",
"journal-title": "Emerg Microbes Infect",
"key": "623_CR26",
"unstructured": "Wang P, et al. SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease. Emerg Microbes Infect. 2020;9:2091–3.",
"volume": "9",
"year": "2020"
},
{
"DOI": "10.15252/emmm.202114122",
"author": "GD de Melo",
"doi-asserted-by": "publisher",
"first-page": "e14122",
"journal-title": "EMBO Mol Med",
"key": "623_CR27",
"unstructured": "de Melo GD, et al. Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin. EMBO Mol Med. 2021;13:e14122.",
"volume": "13",
"year": "2021"
},
{
"DOI": "10.1038/s41598-021-86679-0",
"author": "AP Arévalo",
"doi-asserted-by": "publisher",
"journal-title": "Sci Rep",
"key": "623_CR28",
"unstructured": "Arévalo AP, et al. Ivermectin reduces in vivo coronavirus infection in a mouse experimental model. Sci Rep. 2021;11:7132.",
"volume": "11",
"year": "2021"
},
{
"DOI": "10.1371/journal.ppat.1006955",
"author": "H Namkoong",
"doi-asserted-by": "publisher",
"first-page": "e1006955",
"journal-title": "PLoS Pathog",
"key": "623_CR29",
"unstructured": "Namkoong H, et al. Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia. PLoS Pathog. 2018;14:e1006955.",
"volume": "14",
"year": "2018"
},
{
"DOI": "10.1016/j.ejphar.2021.174191",
"author": "MR Khezri",
"doi-asserted-by": "publisher",
"first-page": "174191",
"journal-title": "Eur J Pharm",
"key": "623_CR30",
"unstructured": "Khezri MR, Zolbanin NM, Ghasemnejad-berenji M, Jafari R. Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection. Eur J Pharm. 2021;905:174191.",
"volume": "905",
"year": "2021"
},
{
"DOI": "10.3389/fimmu.2021.574425",
"author": "VJ Venditto",
"doi-asserted-by": "publisher",
"first-page": "574425",
"journal-title": "Front Immunol",
"key": "623_CR31",
"unstructured": "Venditto VJ, et al. Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19. Front Immunol. 2021;12:574425.",
"volume": "12",
"year": "2021"
},
{
"DOI": "10.3390/microorganisms10122438",
"author": "JM Blondeau",
"doi-asserted-by": "publisher",
"first-page": "2438",
"journal-title": "Microorganisms",
"key": "623_CR32",
"unstructured": "Blondeau JM. Immunomodulatory Effects of Macrolides Considering Evidence from Human and Veterinary Medicine. Microorganisms. 2022;10:2438.",
"volume": "10",
"year": "2022"
},
{
"DOI": "10.1007/s43440-020-00195-y",
"author": "H Kaur",
"doi-asserted-by": "publisher",
"first-page": "736",
"journal-title": "Pharm Rep",
"key": "623_CR33",
"unstructured": "Kaur H, et al. Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes. Pharm Rep. 2021;73:736–49.",
"volume": "73",
"year": "2021"
},
{
"DOI": "10.1016/S0065-2776(08)00003-5",
"author": "T Hirano",
"doi-asserted-by": "publisher",
"first-page": "149",
"journal-title": "Adv Immunol",
"key": "623_CR34",
"unstructured": "Hirano T, et al. Roles of Zinc and Zinc Signaling in Immunity: Zinc as an Intracellular Signaling Molecule. Adv Immunol. 2008;97:149–76.",
"volume": "97",
"year": "2008"
},
{
"DOI": "10.1038/ni.f.220",
"author": "M Vig",
"doi-asserted-by": "publisher",
"first-page": "21",
"journal-title": "Nat Immunol",
"key": "623_CR35",
"unstructured": "Vig M, Kinet JP. Calcium signaling in immune cells. Nat Immunol. 2009;10:21–7.",
"volume": "10",
"year": "2009"
},
{
"DOI": "10.1371/journal.ppat.1001176",
"author": "AJW te Velthuis",
"doi-asserted-by": "publisher",
"first-page": "e1001176",
"journal-title": "PLoS Pathog",
"key": "623_CR36",
"unstructured": "te Velthuis AJW, et al. Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathog. 2010;6:e1001176.",
"volume": "6",
"year": "2010"
},
{
"DOI": "10.1016/j.mehy.2020.109848",
"author": "A Kumar",
"doi-asserted-by": "publisher",
"first-page": "109848",
"journal-title": "Med Hypotheses",
"key": "623_CR37",
"unstructured": "Kumar A, Kubota Y, Chernov M, Kasuya H. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848.",
"volume": "144",
"year": "2020"
},
{
"DOI": "10.1038/ni1373",
"author": "H Kitamura",
"doi-asserted-by": "publisher",
"first-page": "971",
"journal-title": "Nat Immunol",
"key": "623_CR38",
"unstructured": "Kitamura H, et al. Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol. 2006;7:971–7.",
"volume": "7",
"year": "2006"
},
{
"DOI": "10.1038/s41586-022-05594-0",
"author": "T Brevini",
"doi-asserted-by": "publisher",
"first-page": "134",
"journal-title": "Nature",
"key": "623_CR39",
"unstructured": "Brevini T, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2023;615:134–42.",
"volume": "615",
"year": "2023"
},
{
"DOI": "10.1038/ncomms2924",
"author": "L Jin",
"doi-asserted-by": "publisher",
"journal-title": "Nat Commun",
"key": "623_CR40",
"unstructured": "Jin L, et al. The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism. Nat Commun. 2013;4:1937.",
"volume": "4",
"year": "2013"
}
],
"reference-count": 40,
"references-count": 40,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.nature.com/articles/s41429-023-00623-0"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"Drug Discovery",
"Pharmacology"
],
"subtitle": [],
"title": "Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1007/springer_crossmark_policy"
}