Parasite remedy interferes with coronavirus replication

Parasite remedy interferes with coronavirus replication
Parasite remedy interferes with coronavirus replication

The authors of the new study suggested using salicylanilide # 11 to lower viral load and regulate the levels of pro-inflammatory cytokines in Covid-19.

The virus replicates in two membrane layers

Scientists have returned to the search and testing of drugs to treat patients with Covid-19, as the long-term effectiveness of vaccines, according to some, may be in question. The researchers at the Scripps Research Institute and the University of Texas (USA) contributed to this by developing a compound that has shown bidirectional efficacy against coronavirus in laboratory experiments. The results are published in ACS Infectious Disease.

Salicylanilides - a large group of chemical compounds, salicylic acid and aniline amide, used as antiparasitic agents. For the first time, salicylanilides were discovered in Germany in the 1950s and were used to combat helminth infections in cattle. Today, derivatives of these substances, including chlorinated niclosamide, are needed to get rid of tapeworms that can survive in the digestive system.

Later, salicylanides were studied as anticancer and antimicrobial drugs. So, about ten years ago, when strains of gram-positive bacteria Clostridioides difficile caused outbreaks of infectious diarrheal diseases, and antibiotics did not help, scientists created a "library" of about 60 modified salicylanides. Some of them proved to be effective against C. difficile, including compound number 11. But then, as they say, it was put on the back burner due to its toxic effects on the body.

However, when the world was confronted with the Covid-19 pandemic, the authors of the study decided to resume work and once again test the antiviral properties of salicylanilide No. 11. Experiments on mice in the laboratory showed that it helps to fight not only the virus, but also inflammation. The compound can be produced in the form of tablets, and it differs from antihelminthic drugs in its ability to be absorbed into the intestinal walls in order to get to the bloodstream without being toxic.

“The key moment was the antiviral mechanism. The compound blocked the release of viral material from the endosome, and it simply degraded. This process did not make it so easy to create new viral particles, that is, replicate,”the scientists explained.

Salicylanilide No. 11 interfered with endocytosis, the process by which substances, in our case a virus, move into the cell. The endocytosis of the coronavirus, which has bound to the membrane protein ACE2, is organized using lipid rafts - areas of the plasma membrane enriched in glycosphingolipids and cholesterol. Just their cleavage was prevented by salicylanilide. Therefore, since the substance acts inside cells, and not on the S-protein, it can be effective against new strains as well.

In terms of anti-inflammatory properties, salicylanilide helped lower levels of interleukin-6, a pro-inflammatory cytokine that affects many organs and systems in the body. Along with high concentrations of interleukin-1, C-reactive protein and tumor necrosis factor-alpha, it is considered a marker for cytokine storm - a dangerous immune system response that is often fatal in Covid-19.

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