Experiments involving animals and human cells conducted at the University of São Paulo (USP) in Brazil indicate that niclosamide, an anthelmintic widely used against tapeworms, effectively inhibits the replication of SARS-CoV-2 as well as the exacerbated inflammatory response that leads to death. in many people. Patients with severe COVID-19.
More research is needed to see if the effects described in an article published in science progress has been confirmed in patients with the disease, and according to the authors, this will require the development of a new formulation of the drug, since the preparation currently available in pharmacies is taken orally and will not affect the lungs.
Commercially available niclosamide pills are not absorbed by the stomach and therefore act against intestinal worms. They will not be useful to combat COVID-19 if taken orally. To overcome this problem, it will be necessary to develop a formulation that delivers the drug directly to the lungs.”
Zamboni is a Professor at Ribeirão Preto College of Medicine (FMRP-USP) and affiliated with the Research Center for Inflammatory Diseases (CRID), a FAPESP-funded Research, Innovation and Publication Center (RIDC). The study was also funded by FAPESP through 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 inflammasome, a protein complex found on the inside of defense cells. When this cellular machinery is activated, pro-inflammatory molecules called cytokines are produced to warn the immune system of the need to send more defense cells to the site of infection.
Previous research by the FMRP-USP group has shown that inflammation in patients with severe COVID-19 is usually more activated than normal and remains so even after the virus has been eliminated from the organism, causing an exaggerated systemic inflammatory response known as a cytokine storm in the lungs. and other members (More at: agencia.FAPESP.br/39411/).
However, Zamboni stressed that niclosamide should not be used prophylactically to prevent worsening inflammation. “A little bit of inflammation is important for fighting infection by disease-causing microorganisms,” he said. “Excessive inflammation is the problem, as is often the case in severe COVID-19. We do not recommend prophylactic use of the drug, as this may impede the recovery of patients with mild or moderate COVID-19.”
cell cleansing
Niclosamide has been on the market for many years and is primarily prescribed to treat taeniasis (tapeworm infection). It has recently sparked the interest of researchers due to claims that it might work as an antiviral.
According to the authors science progress Article, niclosamide promotes autophagy, a vital process that removes and recycles unwanted or damaged molecules from the body’s cells. When the process of self-cleansing of cells is induced, old organelles are destroyed, cellular components are recycled and inflammatory particles are deactivated. The process also inhibits the replication of SARS-CoV-2 within cells.
The researchers began the study by examining 2,560 compounds, many of which are already used in humans, in search of substances capable of modulating some of the inflammation. This involves infecting human defense cells in the lab Legionella a bacterium known to activate inflammasomes.
After selecting the three most promising drugs, the researchers tested them on mice infected with SARS-CoV-2 and the white blood cells of COVID-19 patients. They also tested the effects of these drugs on macrophages and monocytes, which are front-line immune cells that are extensively involved in inflammatory wounds associated with COVID. Niclosamide has achieved the best results.
To verify its antiviral effect, researchers tested it on monocytes infected in the laboratory with SARS-CoV-2 virus. “The antiviral effect of niclosamide was already known. Indeed, phase 1 clinical trials involving treatment of COVID-19 patients with the drug are currently underway. Our finding that it stimulates autophagy and inhibits inflammation provides additional information on the immune-modulating functions of this very promising drug,” Zamboni said. .
Effects on other diseases
The discovery of an inflammation-suppressing drug opens up new treatments for other conditions that involve inflammation, such as autoimmunity, neurodegenerative disorders, influenza, some types of cancer, and infectious diseases such as Zika, chikungunya and Mayaru fever.
“The study focused on COVID-19, but in theory niclosamide should also enhance the inhibition of inflammation in these other conditions,” Zamboni said. “Our results point to many other research possibilities.”