Anthelmintic inhibits exacerbated inflammatory response related to COVID-19 in preclinical research

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Experiments involving animals and human cells conducted at the University of São Paulo (USP) in Brazil suggest that niclosamide, an anthelmintic widely used against tapeworms, effectively inhibits SARS-CoV-2 replication as well as the exacerbated inflammatory response that leads to death in many patients with severe COVID-19.

More research is needed to find out whether the effects, described in an article published in Science Advances, are confirmed in patients with the disease, and according to the authors this will require the development of a novel formulation of the drug, as the one currently available from pharmacies is orally administered and would not affect the lungs.

The commercially available niclosamide pills aren't absorbed by the stomach and therefore act against intestinal worms. They won't be any use to combat COVID-19 if taken orally. To surmount this problem, it will be necessary to develop a formulation that delivers the drug directly to the lungs."

Dario Zamboni, Last Author

Zamboni is a professor at the Ribeirão Preto Medical School (FMRP-USP) and affiliated with the Center for Research on Inflammatory Diseases (CRID), a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP. The study was also funded by FAPESP via two other projects (19/11342-6 and 20/04964-8).

According to Zamboni, the anti-inflammatory effects of niclosamide observed in the study were due to inhibition of an immune system mechanism known as the inflammasome, a protein complex present in the interior of defense cells. When this cellular machinery is activated, pro-inflammatory molecules called cytokines are produced to warn the immune system that more defense cells need to be sent to the site of the infection.

Previous research by the FMRP-USP group showed that inflammasomes in severe COVID-19 patients are typically more activated than normal and remain so even after the virus has been eliminated from the organism, causing an exaggerated systemic inflammatory response known as a cytokine storm that injures the lungs and other organs (more at:

Zamboni stressed, however, that niclosamide should not be used prophylactically to prevent exacerbated inflammation. "A little inflammation is important to combat infection by pathogenic microorganisms," he said. "Exaggerated inflammation is the problem, as is often the case in severe COVID-19. We're not recommending prophylactic use of the drug, since this could even hinder a recovery by mild or moderate COVID-19 patients."

Cell cleansing

Niclosamide has been on the market for many years and is mainly prescribed to treat taeniasis (tapeworm infection). It has recently aroused interest among researchers due to claims of potential antiviral action.

According to the authors of the Science Advances article, niclosamide promotes autophagy, a vital process that removes and recycles unwanted or damaged molecules from the body's cells. When this process of autophagic cell cleansing is induced, old organelles are destroyed, cellular components are recycled and inflammasomes are deactivated. The process also inhibits replication of SARS-CoV-2 inside cells.

The researchers began the study by screening 2,560 compounds, many of which are already used in humans, in a search for substances capable of inflammasome modulation. This involved infecting human defense cells in vitro with Legionella, a bacterium known for inflammasome activation.

After selecting the three most promising drugs, the researchers tested them on mice infected with SARS-CoV-2 and white blood cells from COVID-19 patients. They also tested the effects of these drugs on macrophages and monocytes, front-line immune cells intensely involved in COVID-related inflammasomes. Niclosamide produced the best results.

To investigate its antiviral action, the researchers tested it on monocytes infected in vitro with SARS-CoV-2. "Niclosamide's antiviral action was already known. Indeed, phase 1 clinical trials involving treatment of COVID-19 patients with the drug are under way right now. Our discovery that it induces autophagy and inhibits inflammasomes offers additional information on the immunomodulatory functions of this highly promising drug," Zamboni said.

Effects on other diseases

The discovery of an inflammasome-inhibiting drug opens up prospects of novel therapies for other conditions involving inflammation, such as autoimmune and neurodegenerative disorders, flu, some kinds of cancer, and infectious diseases such as zika, chikungunya and Mayaro fever.

"The study focused on COVID-19, but in theory niclosamide should also promote inflammasome inhibition in these other cases. Our results point to numerous other research possibilities," Zamboni said.

Journal reference:

de Almeida, L., et al. (2022) Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection. Science Advances.


  1. Frank Collins Frank Collins United States says:

    Oral administration of niclosamide is troublesome unless your target is a tapeworm.  This drug is insoluble in water and barely soluble in alcohol. It also suffers a deleterious  journey through the gut where the enzymes CYP1A2 and UGT1A1 severely degrade this medication.  Little is absorbed into the blood plasma and what’s left fortuitously affects the tapeworm very effectively.  

    Consider the fact there are scores of drugs, insoluble in water and with similar molecular weight to niclosamide, delivered by mouth.  For a variety of clinical reasons, among these are many that are compounded into suppository form for delivery within the rectum.   And they work every efficiently.  

    A rectal suppository mitigates a drug’s exposure to enteric/first-pass hepatic metabolism, improving its bioavailability. The rectal mucosa, richly vascularized by the inferior and middle veins, connect directly to the systemic circulation.  The more proximal superior rectal vein connects to the portal system.  Thus the distal two-thirds of rectal
    mucosa is the optimal target surface area for maximum uptake.

    The literature on niclosamide discloses no attempts to employ a rectal suppository as a delivery system, which makes sense.  Oral administration has worked safely and effectively for half a century.  What would motivate any researcher to test suppositories?  Perhaps current attempts to repurpose this unique drug should go beyond nanotechnology and pulmonary sprays and consider this overlooked mode of administration.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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