Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen
et al., The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z, Jun 2020
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
|
Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin.
Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2.
Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
1.
Mothae et al., SARS-CoV-2 host-pathogen interactome: insights into more players during pathogenesis, Virology, doi:10.1016/j.virol.2025.110607.
2.
Zhang et al., Rho-GTPases subfamily: cellular defectors orchestrating viral infection, Cellular & Molecular Biology Letters, doi:10.1186/s11658-025-00722-w.
3.
Saha et al., Inhaled Dry Powder of Antiviral Agents: A Promising Approach to Treating Respiratory Viral Pathogens, Viruses, doi:10.3390/v17020252.
4.
Ulloa-Aguilar et al., The Nucleolus and Its Interactions with Viral Proteins Required for Successful Infection, Cells, doi:10.3390/cells13181591.
5.
Enyeji et al., Effective Treatment of COVID-19 Infection with Repurposed Drugs: Case Reports, Viral Immunology, doi:10.1089/vim.2024.0034.
6.
Wimalawansa, S., Unlocking Insights: Navigating COVID-19 Challenges and Emulating Future Pandemic Resilience Strategies with Strengthening Natural Immunity, Heliyon, doi:10.1016/j.heliyon.2024.e34691.
7.
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.
8.
Mehraeen et al., Treatments for Olfactory Dysfunction in COVID-19: A Systematic Review, International Archives of Otorhinolaryngology, doi:10.1055/s-0044-1786046.
9.
Scheim et al., Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses, Viruses, doi:10.3390/v16040647.
10.
Yagisawa et al., Global trends in clinical trials of ivermectin for COVID-19—Part 2, The Japanese Journal of Antibiotics, doi:10.11553/antibiotics.77.1_45.
11.
Liu 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.
12.
Scheim (B) 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.
13.
Yemeke et al., Impact of the COVID-19 pandemic on the quality of medical products in Zimbabwe: a qualitative study based on key informant interviews with health system stakeholders, BMJ Open, doi:10.1136/bmjopen-2022-068923.
14.
Kory, P., The Global War on Ivermectin, International Covid Summit III, European Parliament, Brussels, covid19criticalcare.com/wp-content/uploads/2023/05/GLOBAL-WAR-ON-IVERMECTIN-PARLIAMENT.pdf.
15.
Babalola et al., The Place of Ivermectin in the Management of Covid-19: State of the Evidence, Medical Research Archives, doi:10.18103/mra.v11i4.3778.
16.
Loo et al., Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections, Pharmaceutical Research, doi:10.1007/s11095-023-03520-1.
17.
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.
18.
Kory (B), P., The Criminal Censorship of Ivermectin's Efficacy By The High-Impact Medical Journals - Part 1, Pierre Kory’s Medical Musings, pierrekory.substack.com/p/the-criminal-censorship-of-ivermectins.
19.
Al-kuraishy et al., Central effects of Ivermectin in alleviation of Covid-19-induced dysautonomia, Current Drug Targets, doi:10.2174/1389450123666220810102406.
20.
Schwartz, E., Does ivermectin have a place in the treatment of mild Covid-19?, New Microbes and New Infections, doi:10.1016/j.nmni.2022.100989.
21.
Marques et al., Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols, Brazilian Journal of Biology, doi:10.1590/1519-6984.258325.
22.
Semiz, S., SIT1 transporter as a potential novel target in treatment of COVID-19, Biomolecular Concepts, doi:10.1515/bmc-2021-0017.
23.
Zaidi et al., The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review, The Journal of Antibiotics, doi:10.1038/s41429-021-00491-6.
24.
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.
25.
Low et al., Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, doi:10.1016/j.bbadis.2021.166294.
26.
Fordham et al., The uses and abuses of systematic reviews, OSF Preprints, doi:10.31219/osf.io/mp4f2.
27.
Kow et al., Pitfalls in Reporting Sample Size Calculation Across Randomized Controlled Trials Involving Ivermectin for the treatment of COVID-19, American Journal of Therapeutics, doi:10.1097/MJT.0000000000001441.
28.
Santin et al., Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19, New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924.
29.
Adegboro et al., A review of the anti-viral effects of ivermectin, African Journal of Clinical and Experimental Microbiology, doi:10.4314/ajcem.v22i3.2.
30.
Turkia, M., A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021], ResearchGate, doi:10.13140/RG.2.2.16973.36326.
31.
Jagiasi et al., Variation in therapeutic strategies for the management of severe COVID-19 in India- A nationwide cross-sectional survey, The International Journal of Clinical Practice, doi:10.1111/ijcp.14574.
32.
Lind et al., Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis, Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6.
33.
Wang et al., Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19, medRxiv, doi:10.1101/2021.06.01.21258147.
34.
Kory (C) et al., Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19, American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377.
35.
DiNicolantonio et al., Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors, Open Heart, doi:10.1136/openhrt-2021-001655.
36.
Turkia (B), M., A timeline of ivermectin-related events in the COVID-19 pandemic, Research Gate, www.researchgate.net/publication/350610718_A_Timeline_of_Ivermectin-Related_Events_in_the_COVID-19_Pandemic_April_3_2021.
37.
Wehbe et al., Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities, Front. Immunol., doi:10.3389/fimmu.2021.663586.
38.
Yagisawa (B) et al., Global trends in clinical studies of ivermectin in COVID-19, The Japanese Journal of Antibiotics, 74-1, Mar 2021, jja-contents.wdc-jp.com/pdf/JJA74/74-1-open/74-1_44-95.pdf.
39.
Jans et al., The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?, Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.10.042.
40.
Kory (D) et al., Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19, Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369.
41.
Formiga et al., Ivermectin: an award-winning drug with expected antiviral activity against COVID-19, J. Control Release, doi:10.1016/j.jconrel.2020.10.009.
42.
Scheim (D), 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.
43.
Turkia (C), M., FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review, ResearchGate, www.researchgate.net/profile/Mika_Turkia/publication/345694745_FLCCC_Alliance_MATH_ascorbic_acid_and_I-MASK_ivermectin_protocols_for_COVID-19_-_A_Brief_Review/links/5fab010f4585150781078260/FLCCC-Alliance-MATH-ascorbic-acid-and-I-MASK-ivermectin-protocols-for-COVID-19-A-Brief-Review.pdf.
44.
Jans (B) et al., Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?, Cells 2020, 9:9, 2100, doi:10.3390/cells9092100.
45.
Elkholy et al., Ivermectin: A Closer Look at a Potential Remedy, Cureus, doi:10.7759/cureus.10378.
46.
DiNicolantonio (B) et al., Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19, Open Heart, doi:10.1136/openhrt-2020-001350.
47.
Vora et al., White paper on Ivermectin as a potential therapy for COVID-19, Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031.
Heidary et al., 12 Jun 2020, peer-reviewed, 2 authors.
Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen
The Journal of Antibiotics, doi:10.1038/s41429-020-0336-z
Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
Conflict of interest The authors declare that they have no conflict of interest. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Ang, Lee, Choi, Zhang, Lee, Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines, Integr Med Res, doi:10.1016/j.imr.2020.100407.
Atkinson, Audsley, Lieu, Recognition by host nuclear transport proteins drives disorder-to-order transition in Hendra virus V, Sci Rep, doi:10.1038/s41598-017-18742-8
Azeem, Ashraf, Rasheed, Anjum, Hameed, Evaluation of cytotoxicity and antiviral activity of ivermectin against Newcastle disease virus, Pak J Pharm Sci
Baron, Devaux, Colson, Raoult, Rolain, Teicoplanin: an alternative drug for the treatment of COVID-19?, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105944
Barrows, Campos, Powell, A screen of FDAapproved drugs for inhibitors of Zika virus infection, Cell Host Microbe, doi:10.1016/j.chom.2016.07.004.
Bennett, Zhao, Bosard, Imperiale, 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.
Berthomme, Monahan, Parris, Jacquemont, Epstein, Cloning, sequencing, and functional characterization of the two subunits of the pseudorabies virus DNA polymerase holoenzyme: evidence for specificity of interaction, J Virol
Caly, Druce, Catton, Jans, Wagstaff, The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Canga, Prieto, Liébana, Martínez, Vega et al., The pharmacokinetics and interactions of ivermectin in humans-a mini-review, AAPS J
Croci, Bottaro, Chan, Liposomal systems as nanocarriers for the antiviral agent ivermectin, Int J Biomater, doi:10.1155/2016/8043983.
Crump, Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations, J Antibiot
Crump, Ōmura, Ivermectin, 'wonder drug' from Japan: the human use perspective, Proc Jpn Acad Ser B Phys Biol Sci, doi:10.2183/pjab.87.13
Fraser, Rawlinson, Wang, Jans, Wagstaff, Investigating dengue virus nonstructural protein 5 (NS5) nuclear import, Methods Mol Biol, doi:10.1007/978-1-4939-0348-1_19.
Ge, Li, Yang, Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor, Nature, doi:10.1038/nature12711.
Gharebaghi, Heidary, COVID-19 and Iran: swimming with hands tied!, Swiss Med Wkly, doi:10.4414/smw.2020.20242.
Gharebaghi, Heidary, Moradi, Parvizi, Metronidazole; a potential novel addition to the COVID-19 treatment regimen, Arch Academic Emerg Med
Gonzalez Canga, Prieto, Liebana, Martinez, Vega et al., The pharmacokinetics and interactions of ivermectin in humans-a mini-review, AAPS J, doi:10.1208/s12248-007-9000-9.
Gotz, Magar, Dornfeld, Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Sci Rep, doi:10.1038/srep23138.
Ji, Luo, Zika virus NS5 nuclear accumulation is protective of protein degradation and is required for viral RNA replication, Virology, doi:10.1016/j.virol.2019.10.010.
Ketkar, Yang, Wormser, Wang, Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system, Diagn Microbiol Infect Dis, doi:10.1016/j.diagmicrobio.2019.03.012.
Khalil, Samrah, In vivo combined treatment of rats with ivermectin and aged garlic extract attenuates ivermectininduced cytogenotoxicity in bone marrow cells, Res Vet Sci, doi:10.1016/j.rvsc.2018.09.005.
Kircik, Rosso, Layton, Schauber, Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications, J Drugs Dermatol
Kosyna, Nagel, Kluxen, Kraushaar, Depping, The importin alpha/beta-specific inhibitor Ivermectin affects HIFdependent hypoxia response pathways, Biol Chem, doi:10.1515/hsz-2015-0171.
Laing, Devaney, Ivermectin-old drug, new tricks?, Trends Parasitol, doi:10.1016/j.pt.2017.02.004.
Lee, Lee, Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages, Arch Virol, doi:10.1007/s00705-015-2653-2.
Lu, Chang, Potential therapeutic agents against what we know so far, J Chin Med Assoc, doi:10.1097/JCMA.0000000000000318
Lu, Stratton, Tang, Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle, J Med Virol, doi:10.1002/jmv.25678.
Lundberg, Pinkham, Baer, Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan equine encephalitis virus replication, Antivir Res, doi:10.1016/j.antiviral.2013.10.004.
Lv, Liu, Wang, Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo, Antivir Res, doi:10.1016/j.antiviral.2018.09.010.
Mastrangelo, Pezzullo, Burghgraeve, Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, J Antimicrob Chemother, doi:10.1093/jac/dks147.
Raza, Zhai, Ivermectin inhibits bovine herpesvirus 1 DNA polymerase nuclear import and interferes with viral replication, Microorganisms, doi:10.3390/microorganisms8030409
Reviglio, Osaba, Reviglio, Chiaradia, Kuo, COVID-19 and ophthalmology: a new chapter in an old story, Med Hypothesis Disco Innov Ophthalmol
Shechter, Thomas, Lundberg, Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using in silico structure-based-drug-design, Sci Rep, doi:10.1038/s41598-017-17672-9.
Slonska, Cymerys, Skwarska, Golke, Banbura, Influence of importin alpha/beta and exportin 1 on equine herpesvirus type 1 (EHV-1) replication in primary murine neurons, Pol J Vet Sci, doi:10.2478/pjvs-2013-0106.
Sohrabi, Alsafi, Neill, World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19), Int J Surg, doi:10.1016/j.ijsu.2020.02.034.
Surnar, Kamran, Shah, Orally administrable therapeutic synthetic nanoparticle for Zika virus, ACS Nano, doi:10.1021/acsnano.9b02807.
Tay, Fraser, Chan, Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antivir Res, doi:10.1016/j.antiviral.2013.06.002.
Varghese, Kaukinen, Glasker, Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses, Antivir Res, doi:10.1016/j.antiviral.2015.12.012.
Wagstaff, Rawlinson, Hearps, Jans, An AlphaScreen(R)-based assay for high-throughput screening for specific inhibitors of nuclear import, J Biomol Screen, doi:10.1177/1087057110390360.
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem J, doi:10.1042/BJ20120150.
Wang, Du, Huang, The pseudorabies virus DNA polymerase accessory subunit UL42 directs nuclear transport of the holoenzyme, Front Microbiol, doi:10.3389/fmicb.2016.00124.
Wang, Lv, Wang, Qiu, Yang, Ivermectin treatment inhibits the replication of Porcine circovirus 2 (PCV2) in vitro and mitigates the impact of viral infection in piglets, Virus Res, doi:10.1016/j.virusres.2019.01.010.
Yang, Atkinson, Wang, The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer, Antivir Res, doi:10.1016/j.antiviral.2020.104760.
Yang, Hu, Wang, Isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus, J Virol, doi:10.1128/JVI.02582-15.
DOI record:
{
"DOI": "10.1038/s41429-020-0336-z",
"ISSN": [
"0021-8820",
"1881-1469"
],
"URL": "http://dx.doi.org/10.1038/s41429-020-0336-z",
"alternative-id": [
"336"
],
"assertion": [
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Received",
"name": "received",
"order": 1,
"value": "21 April 2020"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Revised",
"name": "revised",
"order": 2,
"value": "5 May 2020"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "Accepted",
"name": "accepted",
"order": 3,
"value": "17 May 2020"
},
{
"group": {
"label": "Article History",
"name": "ArticleHistory"
},
"label": "First Online",
"name": "first_online",
"order": 4,
"value": "12 June 2020"
},
{
"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 that they have no conflict of interest."
},
{
"label": "Free to read",
"name": "free",
"value": "This content has been made available to all."
}
],
"author": [
{
"affiliation": [],
"family": "Heidary",
"given": "Fatemeh",
"sequence": "first"
},
{
"affiliation": [],
"family": "Gharebaghi",
"given": "Reza",
"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": [
[
2020,
6,
12
]
],
"date-time": "2020-06-12T09:04:12Z",
"timestamp": 1591952652000
},
"deposited": {
"date-parts": [
[
2023,
5,
20
]
],
"date-time": "2023-05-20T21:34:06Z",
"timestamp": 1684618446000
},
"indexed": {
"date-parts": [
[
2024,
5,
13
]
],
"date-time": "2024-05-13T13:24:40Z",
"timestamp": 1715606680287
},
"is-referenced-by-count": 225,
"issue": "9",
"issued": {
"date-parts": [
[
2020,
6,
12
]
]
},
"journal-issue": {
"issue": "9",
"published-print": {
"date-parts": [
[
2020,
9
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://www.springer.com/tdm",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
6,
12
]
],
"date-time": "2020-06-12T00:00:00Z",
"timestamp": 1591920000000
}
},
{
"URL": "https://www.springer.com/tdm",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
6,
12
]
],
"date-time": "2020-06-12T00:00:00Z",
"timestamp": 1591920000000
}
}
],
"link": [
{
"URL": "http://www.nature.com/articles/s41429-020-0336-z.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "http://www.nature.com/articles/s41429-020-0336-z",
"content-type": "text/html",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "http://www.nature.com/articles/s41429-020-0336-z.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "297",
"original-title": [],
"page": "593-602",
"prefix": "10.1038",
"published": {
"date-parts": [
[
2020,
6,
12
]
]
},
"published-online": {
"date-parts": [
[
2020,
6,
12
]
]
},
"published-print": {
"date-parts": [
[
2020,
9
]
]
},
"publisher": "Springer Science and Business Media LLC",
"reference": [
{
"DOI": "10.2183/pjab.87.13",
"author": "A Crump",
"doi-asserted-by": "publisher",
"first-page": "13",
"journal-title": "Proc Jpn Acad Ser B Phys Biol Sci.",
"key": "336_CR1",
"unstructured": "Crump A, Ōmura S. Ivermectin, ‘wonder drug’ from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87:13–28. https://doi.org/10.2183/pjab.87.13.",
"volume": "87",
"year": "2011"
},
{
"author": "LH Kircik",
"first-page": "325",
"journal-title": "J Drugs Dermatol",
"key": "336_CR2",
"unstructured": "Kircik LH, Del Rosso JQ, Layton AM, Schauber J. Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications. J Drugs Dermatol. 2016;15:325–32.",
"volume": "15",
"year": "2016"
},
{
"DOI": "10.1208/s12248-007-9000-9.",
"author": "A Gonzalez Canga",
"doi-asserted-by": "publisher",
"first-page": "42",
"journal-title": "AAPS J.",
"key": "336_CR3",
"unstructured": "Gonzalez Canga A, Sahagun Prieto AM, Diez Liebana MJ, Fernandez Martinez N, Sierra Vega M, Garcia Vieitez JJ. The pharmacokinetics and interactions of ivermectin in humans–a mini-review. AAPS J. 2008;10:42–6. https://doi.org/10.1208/s12248-007-9000-9.",
"volume": "10",
"year": "2008"
},
{
"DOI": "10.1016/j.pt.2017.02.004.",
"author": "R Laing",
"doi-asserted-by": "publisher",
"first-page": "463",
"journal-title": "Trends Parasitol.",
"key": "336_CR4",
"unstructured": "Laing R, Gillan V, Devaney E. Ivermectin—old drug, new tricks? Trends Parasitol. 2017;33:463–72. https://doi.org/10.1016/j.pt.2017.02.004.",
"volume": "33",
"year": "2017"
},
{
"DOI": "10.1016/j.ijsu.2020.02.034.",
"author": "C Sohrabi",
"doi-asserted-by": "publisher",
"first-page": "71",
"journal-title": "Int J Surg.",
"key": "336_CR5",
"unstructured": "Sohrabi C, Alsafi Z, O’Neill N, et al. World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19). Int J Surg. 2020;76:71–6. https://doi.org/10.1016/j.ijsu.2020.02.034.",
"volume": "76",
"year": "2020"
},
{
"DOI": "10.1002/jmv.25678.",
"author": "H Lu",
"doi-asserted-by": "publisher",
"first-page": "401",
"journal-title": "J Med Virol",
"key": "336_CR6",
"unstructured": "Lu H, Stratton CW, Tang Y-W. Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. J Med Virol. 2020;92:401–2. https://doi.org/10.1002/jmv.25678.",
"volume": "92",
"year": "2020"
},
{
"DOI": "10.1038/nature12711.",
"author": "X-Y Ge",
"doi-asserted-by": "publisher",
"first-page": "535",
"journal-title": "Nature.",
"key": "336_CR7",
"unstructured": "Ge X-Y, Li J-L, Yang X-L, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503:535–8. https://doi.org/10.1038/nature12711.",
"volume": "503",
"year": "2013"
},
{
"DOI": "10.1128/JVI.02582-15.",
"author": "X-L Yang",
"doi-asserted-by": "publisher",
"first-page": "3253",
"journal-title": "J Virol.",
"key": "336_CR8",
"unstructured": "Yang X-L, Hu B, Wang B, et al. Isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus. J Virol. 2015;90:3253–6. https://doi.org/10.1128/JVI.02582-15.",
"volume": "90",
"year": "2015"
},
{
"DOI": "10.1097/JCMA.0000000000000318",
"doi-asserted-by": "publisher",
"key": "336_CR9",
"unstructured": "Lu C-C, Chen M-Y, Chang Y-L. Potential therapeutic agents against COVID-19: what we know so far. J Chin Med Assoc. 2020. https://doi.org/10.1097/JCMA.0000000000000318."
},
{
"DOI": "10.1016/j.imr.2020.100407.",
"author": "L Ang",
"doi-asserted-by": "publisher",
"first-page": "100407.",
"journal-title": "Integr Med Res.",
"key": "336_CR10",
"unstructured": "Ang L, Lee HW, Choi JY, Zhang J, Soo Lee M. Herbal medicine and pattern identification for treating COVID-19: a rapid review of guidelines. Integr Med Res. 2020;9:100407. https://doi.org/10.1016/j.imr.2020.100407.",
"volume": "9",
"year": "2020"
},
{
"author": "R Gharebaghi",
"first-page": "e40",
"journal-title": "Arch Academic Emerg Med",
"key": "336_CR11",
"unstructured": "Gharebaghi R, Heidary F, Moradi M, Parvizi M. Metronidazole; a potential novel addition to the COVID-19 treatment regimen. Arch Academic Emerg Med. 2020;8:e40.",
"volume": "8",
"year": "2020"
},
{
"DOI": "10.1016/j.ijantimicag.2020.105944",
"doi-asserted-by": "publisher",
"key": "336_CR12",
"unstructured": "Baron SA, Devaux C, Colson P, Raoult D, Rolain J-M. Teicoplanin: an alternative drug for the treatment of COVID-19? Int J Antimicrob Agents. 2020:105944. https://doi.org/10.1016/j.ijantimicag.2020.105944."
},
{
"DOI": "10.4414/smw.2020.20242.",
"author": "R Gharebaghi",
"doi-asserted-by": "publisher",
"first-page": "w20242.",
"journal-title": "Swiss Med Wkly",
"key": "336_CR13",
"unstructured": "Gharebaghi R, Heidary F. COVID-19 and Iran: swimming with hands tied! Swiss Med Wkly. 2020;150:w20242. https://doi.org/10.4414/smw.2020.20242.",
"volume": "150",
"year": "2020"
},
{
"author": "VE Reviglio",
"first-page": "71",
"journal-title": "Med Hypothesis Disco Innov Ophthalmol",
"key": "336_CR14",
"unstructured": "Reviglio VE, Osaba M, Reviglio V, Chiaradia P, Kuo IC. COVID-19 and ophthalmology: a new chapter in an old story. Med Hypothesis Disco Innov Ophthalmol. 2020;9:71–3.",
"volume": "9",
"year": "2020"
},
{
"DOI": "10.1016/j.antiviral.2020.104787",
"doi-asserted-by": "publisher",
"key": "336_CR15",
"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. Antiviral Res. 2020:104787. https://doi.org/10.1016/j.antiviral.2020.104787."
},
{
"DOI": "10.1016/j.chom.2016.07.004.",
"author": "NJ Barrows",
"doi-asserted-by": "publisher",
"first-page": "259",
"journal-title": "Cell Host Microbe",
"key": "336_CR16",
"unstructured": "Barrows NJ, Campos RK, Powell ST, et al. A screen of FDA-approved drugs for inhibitors of Zika virus infection. Cell Host Microbe. 2016;20:259–70. https://doi.org/10.1016/j.chom.2016.07.004.",
"volume": "20",
"year": "2016"
},
{
"DOI": "10.1016/j.diagmicrobio.2019.03.012.",
"author": "H Ketkar",
"doi-asserted-by": "publisher",
"first-page": "38",
"journal-title": "Diagn Microbiol Infect Dis",
"key": "336_CR17",
"unstructured": "Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system. Diagn Microbiol Infect Dis. 2019;95:38–40. https://doi.org/10.1016/j.diagmicrobio.2019.03.012.",
"volume": "95",
"year": "2019"
},
{
"DOI": "10.1016/j.rvsc.2018.09.005.",
"author": "AM Khalil",
"doi-asserted-by": "publisher",
"first-page": "94",
"journal-title": "Res Vet Sci",
"key": "336_CR18",
"unstructured": "Khalil AM, Abu Samrah HM. In vivo combined treatment of rats with ivermectin and aged garlic extract attenuates ivermectin-induced cytogenotoxicity in bone marrow cells. Res Vet Sci. 2018;120:94–100. https://doi.org/10.1016/j.rvsc.2018.09.005.",
"volume": "120",
"year": "2018"
},
{
"DOI": "10.1016/j.virol.2019.10.010.",
"author": "W Ji",
"doi-asserted-by": "publisher",
"first-page": "124",
"journal-title": "Virology.",
"key": "336_CR19",
"unstructured": "Ji W, Luo G. Zika virus NS5 nuclear accumulation is protective of protein degradation and is required for viral RNA replication. Virology. 2020;541:124–35. https://doi.org/10.1016/j.virol.2019.10.010.",
"volume": "541",
"year": "2020"
},
{
"DOI": "10.1016/j.antiviral.2013.06.002.",
"author": "MYF Tay",
"doi-asserted-by": "publisher",
"first-page": "301",
"journal-title": "Antivir Res.",
"key": "336_CR20",
"unstructured": "Tay MYF, Fraser JE, Chan WKK, et al. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antivir Res. 2013;99:301–6. https://doi.org/10.1016/j.antiviral.2013.06.002.",
"volume": "99",
"year": "2013"
},
{
"DOI": "10.1042/BJ20120150.",
"author": "KM Wagstaff",
"doi-asserted-by": "publisher",
"first-page": "851",
"journal-title": "Biochem J.",
"key": "336_CR21",
"unstructured": "Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443:851–6. https://doi.org/10.1042/BJ20120150.",
"volume": "443",
"year": "2012"
},
{
"DOI": "10.1021/acsnano.9b02807.",
"author": "B Surnar",
"doi-asserted-by": "publisher",
"first-page": "11034",
"journal-title": "ACS Nano.",
"key": "336_CR22",
"unstructured": "Surnar B, Kamran MZ, Shah AS, et al. Orally administrable therapeutic synthetic nanoparticle for Zika virus. ACS Nano. 2019;13:11034–48. https://doi.org/10.1021/acsnano.9b02807.",
"volume": "13",
"year": "2019"
},
{
"DOI": "10.1016/j.antiviral.2020.104760.",
"author": "SNY Yang",
"doi-asserted-by": "publisher",
"first-page": "104760",
"journal-title": "Antivir Res.",
"key": "336_CR23",
"unstructured": "Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer. Antivir Res. 2020;177:104760. https://doi.org/10.1016/j.antiviral.2020.104760.",
"volume": "177",
"year": "2020"
},
{
"DOI": "10.1515/hsz-2015-0171.",
"author": "FK Kosyna",
"doi-asserted-by": "publisher",
"first-page": "1357",
"journal-title": "Biol Chem.",
"key": "336_CR24",
"unstructured": "Kosyna FK, Nagel M, Kluxen L, Kraushaar K, Depping R. The importin alpha/beta-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways. Biol Chem. 2015;396:1357–67. https://doi.org/10.1515/hsz-2015-0171.",
"volume": "396",
"year": "2015"
},
{
"DOI": "10.1093/jac/dks147.",
"author": "E Mastrangelo",
"doi-asserted-by": "publisher",
"first-page": "1884",
"journal-title": "J Antimicrob Chemother",
"key": "336_CR25",
"unstructured": "Mastrangelo E, Pezzullo M, De Burghgraeve T, et al. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother. 2012;67:1884–94. https://doi.org/10.1093/jac/dks147.",
"volume": "67",
"year": "2012"
},
{
"DOI": "10.1007/978-1-4939-0348-1_19.",
"author": "JE Fraser",
"doi-asserted-by": "publisher",
"first-page": "301",
"journal-title": "Methods Mol Biol",
"key": "336_CR26",
"unstructured": "Fraser JE, Rawlinson SM, Wang C, Jans DA, Wagstaff KM. Investigating dengue virus nonstructural protein 5 (NS5) nuclear import. Methods Mol Biol. 2014;1138:301–28. https://doi.org/10.1007/978-1-4939-0348-1_19.",
"volume": "1138",
"year": "2014"
},
{
"DOI": "10.1155/2016/8043983.",
"author": "R Croci",
"doi-asserted-by": "publisher",
"first-page": "8043983.",
"journal-title": "Int J Biomater",
"key": "336_CR27",
"unstructured": "Croci R, Bottaro E, Chan KWK, et al. Liposomal systems as nanocarriers for the antiviral agent ivermectin. Int J Biomater. 2016;2016:8043983. https://doi.org/10.1155/2016/8043983.",
"volume": "2016",
"year": "2016"
},
{
"DOI": "10.1038/s41598-017-18742-8",
"author": "SC Atkinson",
"doi-asserted-by": "publisher",
"first-page": "358.",
"journal-title": "Sci Rep.",
"key": "336_CR28",
"unstructured": "Atkinson SC, Audsley MD, Lieu KG. et al. Recognition by host nuclear transport proteins drives disorder-to-order transition in Hendra virus V. Sci Rep. 2018;8:358. https://doi.org/10.1038/s41598-017-18742-8.",
"volume": "8",
"year": "2018"
},
{
"author": "S Azeem",
"first-page": "597",
"journal-title": "Pak J Pharm Sci",
"key": "336_CR29",
"unstructured": "Azeem S, Ashraf M, Rasheed MA, Anjum AA, Hameed R. Evaluation of cytotoxicity and antiviral activity of ivermectin against Newcastle disease virus. Pak J Pharm Sci. 2015;28:597–602.",
"volume": "28",
"year": "2015"
},
{
"DOI": "10.1016/j.antiviral.2013.10.004.",
"author": "L Lundberg",
"doi-asserted-by": "publisher",
"first-page": "662",
"journal-title": "Antivir Res.",
"key": "336_CR30",
"unstructured": "Lundberg L, Pinkham C, Baer A, et al. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan equine encephalitis virus replication. Antivir Res. 2013;100:662–72. https://doi.org/10.1016/j.antiviral.2013.10.004.",
"volume": "100",
"year": "2013"
},
{
"DOI": "10.1038/s41598-017-17672-9.",
"author": "S Shechter",
"doi-asserted-by": "publisher",
"journal-title": "Sci Rep.",
"key": "336_CR31",
"unstructured": "Shechter S, Thomas DR, Lundberg L, et al. Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using in silico structure-based-drug-design. Sci Rep. 2017;7:17705. https://doi.org/10.1038/s41598-017-17672-9.",
"volume": "7",
"year": "2017"
},
{
"DOI": "10.1016/j.antiviral.2015.12.012.",
"author": "FS Varghese",
"doi-asserted-by": "publisher",
"first-page": "117",
"journal-title": "Antivir Res.",
"key": "336_CR32",
"unstructured": "Varghese FS, Kaukinen P, Glasker S, et al. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antivir Res. 2016;126:117–24. https://doi.org/10.1016/j.antiviral.2015.12.012.",
"volume": "126",
"year": "2016"
},
{
"DOI": "10.1038/srep23138.",
"author": "V Gotz",
"doi-asserted-by": "publisher",
"journal-title": "Sci Rep.",
"key": "336_CR33",
"unstructured": "Gotz V, Magar L, Dornfeld D, et al. Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci Rep. 2016;6:23138. https://doi.org/10.1038/srep23138.",
"volume": "6",
"year": "2016"
},
{
"DOI": "10.1007/s00705-015-2653-2.",
"author": "YJ Lee",
"doi-asserted-by": "publisher",
"first-page": "257",
"journal-title": "Arch Virol.",
"key": "336_CR34",
"unstructured": "Lee YJ, Lee C. Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages. Arch Virol. 2016;161:257–68. https://doi.org/10.1007/s00705-015-2653-2.",
"volume": "161",
"year": "2016"
},
{
"DOI": "10.1177/1087057110390360.",
"author": "KM Wagstaff",
"doi-asserted-by": "publisher",
"first-page": "192",
"journal-title": "J Biomol Screen",
"key": "336_CR35",
"unstructured": "Wagstaff KM, Rawlinson SM, Hearps AC, Jans DA. An AlphaScreen(R)-based assay for high-throughput screening for specific inhibitors of nuclear import. J Biomol Screen. 2011;16:192–200. https://doi.org/10.1177/1087057110390360.",
"volume": "16",
"year": "2011"
},
{
"DOI": "10.2478/pjvs-2013-0106.",
"author": "A Slonska",
"doi-asserted-by": "publisher",
"first-page": "749",
"journal-title": "Pol J Vet Sci",
"key": "336_CR36",
"unstructured": "Slonska A, Cymerys J, Skwarska J, Golke A, Banbura MW. Influence of importin alpha/beta and exportin 1 on equine herpesvirus type 1 (EHV-1) replication in primary murine neurons. Pol J Vet Sci. 2013;16:749–51. https://doi.org/10.2478/pjvs-2013-0106.",
"volume": "16",
"year": "2013"
},
{
"DOI": "10.1016/j.antiviral.2018.09.010.",
"author": "C Lv",
"doi-asserted-by": "publisher",
"first-page": "55",
"journal-title": "Antivir Res.",
"key": "336_CR37",
"unstructured": "Lv C, Liu W, Wang B, et al. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antivir Res. 2018;159:55–62. https://doi.org/10.1016/j.antiviral.2018.09.010.",
"volume": "159",
"year": "2018"
},
{
"DOI": "10.1128/jvi.69.5.2811-2818.1995",
"doi-asserted-by": "crossref",
"key": "336_CR38",
"unstructured": "Berthomme H, Monahan SJ, Parris DS, Jacquemont B, Epstein AL. Cloning, sequencing, and functional characterization of the two subunits of the pseudorabies virus DNA polymerase holoenzyme: evidence for specificity of interaction. J Virol. 1995 May;69(5):2811-8. PubMed PMID: 7707503; PubMed Central PMCID: PMC188975"
},
{
"DOI": "10.3389/fmicb.2016.00124.",
"author": "Y-P Wang",
"doi-asserted-by": "publisher",
"first-page": "124.",
"journal-title": "Front Microbiol",
"key": "336_CR39",
"unstructured": "Wang Y-P, Du W-J, Huang L-P, et al. The pseudorabies virus DNA polymerase accessory subunit UL42 directs nuclear transport of the holoenzyme. Front Microbiol 2016;7:124. https://doi.org/10.3389/fmicb.2016.00124.",
"volume": "7",
"year": "2016"
},
{
"DOI": "10.1016/j.virol.2014.10.013.",
"author": "SM Bennett",
"doi-asserted-by": "publisher",
"first-page": "110",
"journal-title": "Virology.",
"key": "336_CR40",
"unstructured": "Bennett SM, Zhao L, Bosard C, Imperiale MJ. Role of a nuclear localization signal on the minor capsid proteins VP2 and VP3 in BKPyV nuclear entry. Virology. 2015;474:110–6. https://doi.org/10.1016/j.virol.2014.10.013.",
"volume": "474",
"year": "2015"
},
{
"DOI": "10.1016/j.virusres.2019.01.010.",
"author": "X Wang",
"doi-asserted-by": "publisher",
"first-page": "80",
"journal-title": "Virus Res.",
"key": "336_CR41",
"unstructured": "Wang X, Lv C, Ji X, Wang B, Qiu L, Yang Z. Ivermectin treatment inhibits the replication of Porcine circovirus 2 (PCV2) in vitro and mitigates the impact of viral infection in piglets. Virus Res. 2019;263:80–6. https://doi.org/10.1016/j.virusres.2019.01.010.",
"volume": "263",
"year": "2019"
},
{
"DOI": "10.3390/microorganisms8030409",
"doi-asserted-by": "publisher",
"key": "336_CR42",
"unstructured": "Raza S, Shahin F, Zhai W, et al. Ivermectin inhibits bovine herpesvirus 1 DNA polymerase nuclear import and interferes with viral replication. Microorganisms. 2020;8. https://doi.org/10.3390/microorganisms8030409."
},
{
"key": "336_CR43",
"unstructured": "The FDA’s Center for Veterinary Medicine, https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-humans. Accessed 5 May 2020."
},
{
"DOI": "10.1208/s12248-007-9000-9",
"author": "AG Canga",
"doi-asserted-by": "publisher",
"first-page": "42",
"journal-title": "AAPS J",
"key": "336_CR44",
"unstructured": "Canga AG, Prieto AM, Liébana MJ, Martínez NF, Vega MS, Vieitez JJ. The pharmacokinetics and interactions of ivermectin in humans—a mini-review. AAPS J. 2008;10:42–6.",
"volume": "10",
"year": "2008"
},
{
"DOI": "10.1038/ja.2017.11",
"author": "A Crump",
"doi-asserted-by": "publisher",
"first-page": "495",
"journal-title": "J Antibiot",
"key": "336_CR45",
"unstructured": "Crump A. Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations. J Antibiot. 2017;70:495–505.",
"volume": "70",
"year": "2017"
}
],
"reference-count": 45,
"references-count": 45,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.nature.com/articles/s41429-020-0336-z"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1007/springer_crossmark_policy",
"volume": "73"
}
