Experiments with animals and human cells conducted at the University of São Paulo (USP) in Brazil showed that niclosamide, a widely used anthelmintic opposed to tapeworms, well inhibits SARS-CoV-2 replication, as well as exacerbated inflammatory reaction leading to death in many cases of patients with severe COVID-19.
More studies are needed to know if the effects, described in a paper published in Science Advances, manifest themselves in patients with the disease, and according to the authors, this will require the progression of new formulations of the drug, as the Lately it is held in pharmacies is administered orally and not by the lungs.
Commercially available niclosamide tablets are not absorbed by the abdomen and act against pinworms. They will not be helpful in fighting COVID-19 if taken orally. To overcome this problem, it will be mandatory to expand the formulas that offer the drug directly to the lungs. “
Zamboni is a professor at the Medical School of Ribeirão Preto (FMRP-USP) and affiliated with the Inflammatory Diseases Research Center (CRID), a research, innovation and dissemination center (RIDC) funded through FAPESP. The study also financed via FAPESP via two other projects (19/11342-6 and 20/04964-8).
According to Zamboni, the anti-inflammatory effects of niclosamide seen in the study were due to inhibition of an immune formula mechanism known as inflammasome, a protein complex discovered in internal defense cells. When this cellular machinery is activated, pro-inflammatory molecules called cytokines are activated. Produced to warn the immune formula that more defense cells want to be sent to the site of infection.
Previous studies through the FMRP-USP organization have shown that inflammasomes in patients with severe COVID-19 are more activated than usual and remain so even after the virus is cleared from the body, causing an exaggerated systemic inflammatory reaction known as cytokine typhoon that injures the lungs and other organs (more about: agencia. fapesp. br/39411/).
However, Zamboni stressed that niclosamide does not deserve to be used prophylactically to prevent exacerbated inflammation. “A little inflammation is vital to fight infection with pathogenic microorganisms,” he said. “Exaggerated inflammation is the problem, as is the case in severe cases of COVID-19. We are not proposing prophylactic use of the drug, as this would possibly even obstruct the recovery of patients with mild or moderate COVID-19. “
Niclosamide has been on the market for many years and is basically prescribed to treat taeniasis (tapeworm infection). Recently, it has attracted the interest of researchers due to claims of a possible antiviral action.
According to the authors of the Science Advances article, niclosamide promotes autophagy, an important procedure that recycles broken or unwanted molecules from the body’s cells. When this autophagic cell cleansing procedure is induced, old organelles are destroyed, cell parts are recycled and inflamed and deactivated. The procedure also inhibits the replication of SARS-CoV-2 inner cells.
The researchers began the study by analyzing 2,560 compounds, many of which are already used in humans, for ingredients that can modulate the inflammasome. The goal is to infect human defense cells in vitro with Legionella, a bacterium known to activate the inflammasome.
After deciding on the 3 most promising drugs, the researchers tested them on mice inflamed with SARS-CoV-2 and white blood cells from COVID-19 patients. They also tested the effects of those drugs on macrophages and monocytes, first-line immune cells. Intensely concerned about inflammasomes related to COVID. La niclosamide gave the results.
To examine its antiviral action, the researchers tested it on inflamed monocytes in vitro with SARS-CoV-2. “The antiviral action of niclosamide was already known. In fact, Phase 1 clinical trials involving the COVID-19 patient remedy with the drug are ongoing right now. Our discovery that it induces autophagy and inhibits inflammasomes provides further insight into the immunomodulatory purposes of this very promising drug,” Zamboni said.
The discovery of an inflammasome inhibitor drug opens customers to new treatments for other situations involving inflammation, such as autoimmune and neurodegenerative diseases, influenza, cancer insurance, and infectious diseases such as Zika, chikungunya and Mayaro fever.
“The study focused on COVID-19, but in theory, niclosamide also promotes inflammation inhibition in those other cases. Our findings point to many other possibilities for study,” Zamboni said.
São Paulo Research Foundation (FAPESP)
de Almeida, L. , et al. (2022) Identification of immunomodulatory drugs that inhibit inflammasomes and adjust SARS-CoV-2 infection. Progress scientifiques. doi. org/10. 1126/sciadv. abo5400.
News-Medical. net – An AZoNetwork website
Owned and operated through AZoNetwork, © 2000-2022