TRIESTE. Originally, fifty years ago, it was a pesticide that farmers used to kill snails. Now Niclosamide, also used to treat intestinal infections caused by tapeworms, is recycled as a drug capable of warding off the harmful effects that the Spike protein of Sars-Cov-2 causes to cells, thus blocking the damage caused to the lungs.
The research was conducted on the Trieste-London axis in the laboratories of King’s College London and the International Center for Genetic Engineering and Biotechnology (Icgeb) in the Area Science Park, in collaboration with the Institute of Pathological Anatomy of the University of Trieste and of the Biophysics Institute of the Cnr of Trento, under the direction of the Trieste scientist Mauro Jacket.
The team of researchers, using robotic screening of over three thousand drugs, hunted for the “right” one. And he identified it, going by exclusion, after a long investigation. At that point the research group wanted to understand why Niclosamide worked in an organism affected by Covid, while other drugs were ineffective, thus discovering the mechanism that leads to the fusion of cells infected with Sars-Cov-2 and the substance that can stop this process.
«It is the most effective drug we have discovered to block TMEM16 and the formation of syncytium (the multinucleated protoplasmic mass formed by the secondary meeting of previously separated cells, pictured above). Niclosamide has a low cost and is safe. With our data, a clinical trial with niclosamide in India on 120 people is starting these days ”, explains enthusiastically Jacket, for more than a year engaged in the laboratory in the daily battle to stem the virus. The research has just been published in the scientific journal Nature.
«It’s a great result but now we need caution. The tests carried out in the laboratory have all given positive and encouraging results, but we await the response of the human experimentation, which will take about three months, ”says Jacket. «Niclosamide could prove to be decisive in cases of people heavily attacked by the virus so as to require hospital care, but still not so serious as to resort to intensive care. Technically this drug is able to stop the harmful effects that the Spike protein of Sars-CoV-2 causes to the cells and therefore could block bilateral pneumonia and thrombosis in the lungs which are the main causes of mortality “, observes the researcher .
The same group of researchers, in November last year, in an article published on Lancet eBioMedicinand had written that the lungs of patients who died from Covid-19, in addition to showing extensive damage and the presence of clots that block blood circulation, contain a vast number of abnormal cells, very large and with many nuclei, infected with the virus even after 30-40 days of hospitalization. These cells result from the ability of the coronavirus Spike protein to stimulate the fusion of infected cells with neighboring cells. Stimulated by these observations, the researchers began their investigation.
«We are very excited by our results – says Mauro Jacket – for at least two reasons. First, because we have discovered an entirely new mechanism, activated by the Spike protein and important to the virus. Our research shows that Spike activates a family of cell proteins, called TMEM16, which are essential for cell fusion. Second, because this mechanism also underlies platelet activation, and could therefore also explain why 70% of patients with severe Covid-19 develop thrombosis. And now we know that there is at least one drug, Niclosamide, capable of blocking this mechanism ».
Niclosamide is a drug synthesized in the 1970s and used since 1982 for the treatment of intestinal infections due to tapeworms, the worm that enters the body. The new study shows how this drug, by inhibiting TMEM16 and cell fusion, also blocks the replication of the virus. “I think this research is important – continues Jacket – also because it shifts attention from the attempt to block the multiplication of the virus, as up to now, drugs such as Remdesivir have tried to do, with little success, to that of inhibiting the damage caused to the virus. organism from infected cells. I am increasingly convinced that Covid-19 is a disease caused not by the simple destruction of cells infected by the virus, but by the persistence of these cells in the body for long periods of time. The mechanism that we have discovered could therefore also be involved in the development of the so-called long Covid, that is, explain the difficulty that many patients have in recovering after the disease “.
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