Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All ivermectin studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19ivm.org COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Niclosamide and ivermectin modulate caspase-1 activity and proinflammatory cytokine secretion in a monocytic cell line

Munson et al., British Society For Nanomedicine Early Career Researcher Summer Meeting, 2021
Jun 2021  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
In Vitro study showing potential therapeutic effects of ivermectin and niclosamide on the immune system by reducing inflammation and modulating key proteins involved in the inflammatory response. Ivermectin and niclosamide reduced proinflammatory markers and NLRP3 formation, and reduced caspase-1 activity.
68 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 H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Munson et al., 16 Jun 2021, preprint, 5 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Niclosamide and ivermectin modulate caspase-1 activity and proinflammatory cytokine secretion in a monocytic cell line
Micheal C Munson, Danielle Brain, Christopher David, Andrew Owen, Dr Neill J Liptrott
The COVID-19 pandemic has led to an unprecedented demand for new and repurposed therapeutics to ameliorate the morbidity and mortality associated with SARS-CoV-2 infection. However, there is still a paucity of information relating to successful antiviral compounds. The repurposing of immune modulators, such as dexamethasone and tocilizumab, has shown significant improvement in survival rates. Repurposing of small molecules that may have antiviral and immunomodulatory potential may have significant impact on the pandemic. Niclosamide and ivermectin are being investigated for repurposing as potential treatments for COVID-19 patients. Both niclosamide and ivermectin have been proposed and studied based upon possible immunomodulatory and antiviral activity. To improve their posology, there are also ongoing efforts to nano-formulate these drugs, but a much greater understanding of their mechanisms of action is required to rationalise their plausibility as candidates. We have previously shown that niclosamide can affect responses to immune stimulation in ex vivo cells from healthy rats exposed via a long-acting injectable formulation. The current study aimed to further understand the effects of niclosamide and ivermectin on inflammasome activity in human cells due to the involvement of inflammasomes in the hyperinflammation and coagulation observed in severely ill COVID-19 patients. Caspase-1 activity and proinflammatory cytokine secretion in THP1 cells exposed to physiologically-relevant concentrations of niclosamide and ivermectin were measured as markers of inflammasome activity. Exposure to both niclosamide and ivermectin led to lower caspase-1 activity compared to untreated cells as well as resulting in lower secretion of IL-1β, IL-18, and TNF-α if treated prior to LPS induction. These data in their own right should not be interpreted as being a conclusive indicator of the utility of these drugs in COVID-19. However, the data presented suggests a putative mechanism for the proposed immune modulation. Substantive further work is still needed to determine the precise mechanism(s) that underpin these findings and whether the observations are relevant in vivo.
References
Arshad, Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics, Clinical Pharmacology & Therapeutics
Baker, A call for the appropriate application of clinical pharmacological principles in the search for safe and efficacious COVID-19 (SARS-COV-2) treatments, British Journal of Clinical Pharmacology
Cavalcanti, Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19, New England Journal of Medicine, doi:10.1056/NEJMoa2019014
Chen, Clinical and immunological features of severe and moderate coronavirus disease 2019, J Clin Invest
Hobson, Scalable nanoprecipitation of niclosamide and in vivo demonstration of long-acting delivery after intramuscular injection, Nanoscale
Junqueira, SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release, doi:10.1101/2021.03.06.21252796
Liang, Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis, Inflamm Res
Merad, Martin, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nature Reviews Immunology
Muñoz, Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers, Nature Reviews Immunology
Pinho, EMA recommends COVID-19 Vaccine AstraZeneca for authorisation in the EU
Pneumonia, None, New England Journal of Medicine
Prabhakara, Niclosamide inhibits SARS-CoV2 entry by blocking internalization through pH-dependent CLIC/GEEC endocytic pathway, bioRxiv, doi:10.1101/2020.12.16.422529
Qin, Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China, Clin Infect Dis
Rannard, Chasing COVID-19 chemotherapeutics without putting the cart before the horse, British Journal of Clinical Pharmacology n/a
Salama, Tocilizumab in Patients Hospitalized with Covid-19
Schweizer, A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer, PLoS One
Skipper, Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial, Ann Intern Med
Thi Tran, Kitami, Niclosamide activates the NLRP3 inflammasome by intracellular acidification and mitochondrial inhibition, Communications Biology
Wu, Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide, Antimicrob Agents Chemother
Yang, Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors, Cell Death & Disease
Yao, Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis
Zhang, Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflamm. res
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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.
  or use drag and drop   
Submit