Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment

Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055

Sep 2020

Source PDF All Studies Meta AnalysisMeta

In Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV.

Authors note that the combination of ivermectin and other drugs might result in more favorable prognoses for patients with COVID-19, for example ivermerctin and HCQ.

57 preclinical studies support the efficacy of ivermectin for COVID-19:

20 In Vitro studies Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Liu (B), Mody, Mountain Valley MD, Munson, Saha (B), Segatori, Surnar, Yesilbag, Zhang, Zheng

13 In Vivo animal studies Abd-Elmawla, Albariqi, Arévalo, Chaccour, de Melo, Errecalde, Ma, Madrid, Mountain Valley MD, Uematsu, Yan, Zhang, Zheng

Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.

Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CL^pro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.

Important missing comments or errors? Let us know.

1. 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.springer.com, doi.org.

2. 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.sciencedirect.com, doi.org.

3. 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.sciencedirect.com, doi.org.

4. Aminpour et al., In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds, Computation, doi:10.3390/computation10040051.mdpi.com, doi.org.

5. Arévalo et al., Ivermectin reduces in vivo coronavirus infection in a mouse experimental model, Scientific Reports, doi:10.1038/s41598-021-86679-0.nature.com, doi.org.

6. 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.sciencedirect.com, doi.org.

7. 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.tandfonline.com, doi.org.

8. 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.sciencedirect.com, doi.org.

9. 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.biorxiv.org, doi.org.

10. 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.sciencedirect.com, doi.org.

11. 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.nature.com, doi.org.

12. 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.sciencedirect.com, doi.org.

13. 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.futuremedicine.com, doi.org.

14. Croci et al., Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin, International Journal of Biomaterials, doi:10.1155/2016/8043983.hindawi.com, doi.org.

15. 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.plos.org, doi.org.

16. 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.embopress.org, doi.org.

17. 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.mdpi.com, doi.org.

18. Descotes, J., Medical Safety of Ivermectin, ImmunoSafe Consultance, www.medincell.com/wp-content/uploads/2021/03/Clinical_Safety_of_Ivermectin-March_2021.pdf.medincell.com.

19. 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.bmj.com, doi.org.

20. DiNicolantonio (B) 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.bmj.com, doi.org.

21. 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.sciencedirect.com, doi.org.

22. 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.frontiersin.org, doi.org.

23. 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.rsc.org, doi.org.

24. 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.chemrxiv.org, doi.org.

25. 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.sciencedirect.com, doi.org.

26. 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.sciencedirect.com, doi.org.

27. Götz et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Scientific Reports, doi:10.1038/srep23138.nature.com, doi.org.

28. 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.sciencedirect.com, doi.org.

29. Jitobaom 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.biomedcentral.com, doi.org.

30. Jitobaom (B) 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.researchsquare.com, doi.org.

31. Kern et al., Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing, Frontiers in Pharmacology, doi:10.3389/fphar.2021.625678.frontiersin.org, doi.org.

32. Kosyna et al., The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biological Chemistry, doi:10.1515/hsz-2015-0171.degruyter.com, doi.org.

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.iiarjournals.org, doi.org.

34. 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.wiley.com, doi.org.

35. 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.biomedcentral.com, doi.org.

36. 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.sciencedirect.com, doi.org.

37. Ma et al., Ivermectin contributes to attenuating the severity of acute lung injury in mice, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113706.sciencedirect.com, doi.org.

38. 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.sciencedirect.com, doi.org.

39. 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.oup.com, doi.org.

40. 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.nature.com, doi.org.

41. 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.globenewswire.com.

42. 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.archive.org.

43. 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.scitechnol.com.

44. 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.wiley.com, doi.org.

45. 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.tandfonline.com, doi.org.

46. 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.researchsquare.com, doi.org.

47. 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.researchsquare.com, doi.org.

48. Saha (B) et al., Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder, Pharmaceutics, doi:10.3390/pharmaceutics14071432.mdpi.com, doi.org.

49. 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.researchsquare.com, doi.org.

50. 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.mdpi.com, doi.org.

51. Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, MDPI AG, doi:10.20944/preprints202005.0439.v3.preprints.org, doi.org.

52. Surnar et al., Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19, ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179.acs.org, doi.org.

53. 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.researchsquare.com, doi.org.

54. 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.sciencedirect.com, doi.org.

55. 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.springer.com, doi.org.

56. 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.nature.com, doi.org.

57. 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.teknolabjournal.com, doi.org.

58. 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.sciencedirect.com, doi.org.

59. Vottero et al., Computational Prediction of the Interaction of Ivermectin with Fibrinogen, Molecular Sciences, doi:10.3390/ijms241411449.mdpi.com, doi.org.

60. 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.portlandpress.com, doi.org.

61. Wagstaff (B) et al., An AlphaScreen®-Based Assay for High-Throughput Screening for Specific Inhibitors of Nuclear Import, SLAS Discovery, doi:10.1177/1087057110390360.sciencedirect.com, doi.org.

62. Yan et al., Anti-inflammatory effects of ivermectin in mouse model of allergic asthma, Inflammation Research, doi:10.1007/s00011-011-0307-8.springer.com, doi.org.

63. 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.sciencedirect.com, doi.org.

64. 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.sciencedirect.com, doi.org.

65. 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.springer.com, doi.org.

66. 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.frontiersin.org, doi.org.

67. 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.sciencedirect.com, doi.org.

Li et al., 22 Sep 2020, peer-reviewed, 3 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

All Studies Meta Analysis Submit Updates or Corrections

This Paper Ivermectin All

Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment

Na Li, Lingfeng Zhao, Xianquan Zhan

Journal of Cellular Physiology, doi:10.1002/jcp.30055

Viruses such as human cytomegalovirus (HCMV), human papillomavirus (HPV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) represent a great burden to human health worldwide. FDA-approved anti-parasite drug ivermectin is also an antibacterial, antiviral, and anticancer agent, which offers more potentiality to improve global public health, and it can effectively inhibit the replication of SARS-CoV-2 in vitro. This study sought to identify ivermectin-related virus infection pathway alterations in human ovarian cancer cells. Stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics was used to analyze human ovarian cancer cells TOV-21G treated with and without ivermectin (20 μmol/L) for 24 h, which identified 4447 ivermectin-related proteins in ovarian cancer cells. Pathway network analysis revealed four statistically significant antiviral pathways, including HCMV, HPV, EBV, and HIV1 infection pathways. Interestingly, compared with the reported 284 SARS-CoV-2/COVID-19-related genes from GencLip3, we identified 52 SARS-CoV-2/COVID-19-related protein alterations when treated with and without ivermectin. Protein-protein network (PPI) was constructed based on the interactions between 284 SARS-CoV-2/COVID-19-related genes and between 52 SARS-CoV-2/COVID-19-related proteins regulated by ivermectin. Molecular complex detection analysis of PPI network identified three hub modules, including cytokines and growth factor family, MAP kinase and G-protein family, and HLA class proteins. Gene Ontology analysis revealed 10 statistically significant cellular components, 13 molecular functions, and 11 biological processes. These findings demonstrate the broad-spectrum antiviral property of ivermectin benefiting for COVID-19 treatment in the context of predictive, preventive, and personalized medicine in virus-related diseases.

CONFLICT OF INTERESTS The authors have declared that no competing interests exist. AUTHOR CONTRIBUTIONS Na Li performed SILAC cell experiments, analyzed the data, prepared figures and tables, and drafted the manuscript. Lingfeng Zhao participated in bioinformatics analysis. Xianquan Zhan conceived the concept, guided experiments and data analysis, supervised results, wrote and critically revised the manuscript, and was responsible for the financial supports and corresponding works. All authors approved the final manuscript. ORCID Xianquan Zhan http://orcid.org/0000-0002-4984-3549 SUPPORTING INFORMATION Additional Supporting Information may be found online in the supporting information tab for this article. How to cite this article: Li N, Zhao L, Zhan X. Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021;236:2959-2975. https://doi.org/10.1002/jcp.30055

References

Abdeltawab, Rifaie, Shoeib, El-Latif, Badawi et al., Insights into the impact of Ivermectin on some protein aspects linked to Culex pipiens digestion and immunity, Parasitology Research

Almeida, Queiroz, Sousa, Sousa, Cervical cancer and HPV infection: Ongoing therapeutic research to counteract the action of E6 and E7 oncoproteins, Drug Discovery Today

Alpalhão, Ferreira, Filipe, Persistent SARS-CoV-2 infection and the risk for cancer, Medical Hypotheses

Andoniou, Degli-Esposti, Insights into the mechanisms of CMV-mediated interference with cellular apoptosis, Immunology and Cell Biology

Ashour, Ivermectin: From theory to clinical application, International Journal of Antimicrobial Agents

Athanasiou, Bowden, Paraskevaidi, Fotopoulou, Martin-Hirsch et al., HPV vaccination and cancer prevention, Best Practice & Research Clinical Obstetrics & Gynaecology

Bader, Hogue, An automated method for finding molecular complexes in large protein interaction networks, BMC Bioinformatics

Benvenuto, Giovanetti, Ciccozzi, Spoto, Angeletti et al., The 2019-new coronavirus epidemic: Evidence for virus evolution, Journal of Medical Virology

Bindea, Mlecnik, Hackl, Charoentong, Tosolini et al., ClueGO: A cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks, Bioinformatics

Bojkova, Klann, Koch, Widera, Krause et al., Proteomics of SARS-CoV-2-infected host cells reveals therapy targets, Nature

Boussinesq, Ivermectin, Medecine tropicale

Britt, Manifestations of human cytomegalovirus infection: Proposed mechanisms of acute and chronic disease, Current Topics in Microbiology and Immunology

Buechner, Common skin disorders of the penis, BJU International

Burg, Miller, Baker, Birnbaum, Currie et al., Avermectins, new family of potent anthelmintic agents: Producing organism and fermentation, Antimicrobial Agents Chemother

Buxmann, Hamprecht, Meyer-Wittkopf, Friese, Primary human cytomegalovirus (HCMV) infection in pregnancy, Deutsches Ärzteblatt International

Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research

Chabala, Mrozik, Tolman, Eskola, Lusi et al., Ivermectin, a new broad-spectrum antiparasitic agent, Journal of Medicinal Chemistry

Chaccour, Hammann, Ramón-García, Rabinovich, Ivermectin and COVID-19: Keeping rigor in times of urgency, American Journal of Tropical Medicine and Hygiene

Crump, Ivermectin: Enigmatic multifaceted 'wonder' drug continues to surprise and exceed expectations, Journal of Antibiotics

Csóka, Németh, Szabó, Davies, Varga et al., Macrophage P2X4 receptors augment bacterial killing and protect against sepsis, JCI Insight

Deng, Xu, Long, Xie, Suppressing ROS-TFE3-dependent autophagy enhances ivermectin-induced apoptosis in human melanoma cells, Journal of Cellular Biochemistry, doi:10.1002/jcb.27490

Develoux, None

Diao, Cheng, Zhao, Xu, Dong et al., Ivermectin inhibits canine mammary tumor growth by LI ET AL. | 2973 regulating cell cycle progression and WNT signaling, BMC Veterinary Research

Dou, Chen, Wang, Yuan, Lei et al., Ivermectin induces cytostatic autophagy by blocking the PAK1/Akt axis in breast cancer, Cancer Research

Gallardo, Mariamé, Gence, Tilkin-Mariamé, Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth, Drug Design, Development and Therapy

Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, Journal of Clinical Pharmacology

He, Ding, Zhang, Che, He et al., Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS, Journal of Pathology

Holder, Grant, Human cytomegalovirus IL-10 augments NK cell cytotoxicity, Journal of Leukocyte Biology

Hoppe-Seyler, Bossler, Braun, Herrmann, Hoppe-Seyler, The HPV E6/E7 Oncogenes: Key factors for viral carcinogenesis and therapeutic targets, Trends in Microbiology

Huynh, Gulick, HIV prevention. Treasure Island

Jiang, Wang, Sun, Wu, Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway, Journal of Experimental and Clinical Cancer Research

Juarez, Schcolnik-Cabrera, Dueñas-Gonzalez, The multitargeted drug ivermectin: From an antiparasitic agent to a repositioned cancer drug, American Journal of Cancer Research

Lai, Shih, Ko, Tang, Hsueh, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges, International Journal of Antimicrobial Agents

Laing, Gillan, Devaney, Ivermectin-Old drug, new tricks?, Trends Parasitol

Lee, Lim, Ham, Kim, You et al., Ivermectin induces apoptosis of porcine trophectoderm and uterine luminal epithelial cells through loss of mitochondrial membrane potential, mitochondrial calcium ion overload, and reactive oxygen species generation, Pesticide Biochemistry and Physiology

Letko, Marzi, Munster, Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses, Nature Microbiology

Levy, Martin, Bursztejn, Chiaverini, Miquel et al., Ivermectin safety in infants and children under 15 kg treated for scabies: A multicentric observational study, British Journal of Dermatology

Li, Zhan, Anti-parasite drug ivermectin can suppress ovarian cancer by regulating lncRNA-EIF4A3-mRNA axes, EPMA Journal

Li, Zhou, Zhang, Wang, Zhao et al., Updated Approaches against SARS-CoV-2, Antimicrob Agents Chemother

Lv, Liu, Wang, Dang, Qiu et al., Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo, Antiviral Research

Marques-Piubelli, Salas, Pachas, Becker-Hecker, Vega et al., Epstein-Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: A review, Pathology

Nash, Robertson, How to evolve the response to the global HIV epidemic with new metrics and targets based on pretreatment CD4 counts, Current HIV/AIDS Reports

Nicolas, Maia, Bassat, Kobylinski, Monteiro et al., Safety of oral ivermectin during pregnancy: A systematic review and meta-analysis, Lancet Global Health

Nussinovitch, Prais, Volovitz, Shapiro, Amir, Post-infectious acute cerebellar ataxia in children, Clinical Pediatrics

Patrì, Fabbrocini, Hydroxychloroquine and ivermectin: A synergistic combination for COVID-19 chemoprophylaxis and treatment?, Journal of the American Academy of Dermatology

Rappsilber, Ishihama, Mann, Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics, Analytical Chemistry

Rehwinkel, Gack, RIG-I-like receptors: Their regulation and roles in RNA sensing, Nature Reviews Immunology

Rezk, Zhao, Weiss, Epstein-Barr virus (EBV)-associated lymphoid proliferations, a 2018 update, Human Pathology

Schaller, Gonser, Belge, Braunsdorf, Nordin et al., Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea, Journal of the European Academy of Dermatology and Venereology

Shannon-Lowe, Rowe, Epstein Barr virus entry; kissing and conjugation, Current Opinion in Virology

Szklarczyk, Franceschini, Wyder, Forslund, Heller et al., STRING v10: Protein-protein interaction networks, integrated over the tree of life, Nucleic Acids Research

Ulrich, Pillat, CD147 as a target for COVID-19 treatment: Suggested effects of azithromycin and stem cell engagement, Stem Cell Reviews and Reports

Van Wyk, Malan, Resistance of field strains of Haemonchus contortus to ivermectin, closantel, rafoxanide and the benzimidazoles in South Africa, Veterinary Record

Varghese, Kaukinen, Gläsker, Bespalov, Hanski et al., Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses, Antiviral Research

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, Biochemical Journal

Wang, Zhao, Wang, Wen, Jiang et al., GenCLiP 3: Mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing, Bioinformatics

Wei, Zang, Li, Zhang, Gao et al., Grouper PKR activation inhibits red-spotted grouper nervous necrosis virus (RGNNV) replication in infected cells, Developmental and Comparative Immunology

Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer, Antiviral Research

Yu, Wang, Han, He, ClusterProfiler: An R package for comparing biological themes among gene clusters, OMICS

Zavattoni, Furione, Arossa, Iasci, Spinillo et al., Diagnosis and counseling of fetal and neonatal HCMV infection, Early Human Development

Zhang, Song, Xiong, Ci, Li et al., Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages, International Immunopharmacology

Zhang, Wang, Wang, Zheng, Herpes simplex virus 1 E3 ubiquitin ligase ICP0 protein inhibits tumor necrosis factor alpha-induced NF-κB activation by interacting with p65/RelA and p50/NF-κB1, Journal of Virology

Download Image

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit

@CovidAnalysis

FAQ

Public domain CC0 1.0