According to a new online publication in the journal ACS Infectious Disease, a tapeworm treatment group has been reformulated to show two-pronged effectiveness against COVID-19.This compound is part of a group of molecules called salicylanilides and was created in the laboratory of Professor Kim Janda (PhD), the Ely R. Callaway Jr. Professor of Chemistry and director at Scripps Research's Worm Institute for Research and Medicine, La Jolla (CA).Janda states that salicylanilides have been proven to be effective against certain viruses for at least 10 to 15 years. However, they can cause toxicity and are often gut-restricted.Janda's compound is able to overcome both these issues in cell-based and mouse-based testing. It acts as an antiviral drug-like compound and an anti-inflammatory compound-like compound with properties that make it suitable for use in pill form.Salicylanilides were discovered for the first time in Germany in 1950s. They were used to treat worm infections in cattle. To treat tapeworm, animals and humans use niclosamide as well as other versions. They are also known to have anti-cancer properties and antimicrobial capabilities.Janda's modified salicylanilide compound was one of 60 he had previously created years ago for another project. He discovered that the compounds may have antiviral properties and began screening them in cells with collaborators from Sorrento Therapeutics, The University of Texas Medical Branch and, later, with John Teijaro (Scripps Research immunologist), who did rodent studies.AdvertisementOne compound stood out. Simply called "No. It is simply called "No. 11". It differs from commercial tapeworm medications in key ways. This includes its ability to pass beyond your gut and be absorbed into your bloodstream -- without worrying about toxic effects.Janda states that niclosamide is primarily digestive-track restricted. This makes sense because parasites live in that area. "Repurposing a drug for COVID would be counterintuitive. You want something that is easily bioavailable and does not have the systemic toxicities that niclosamide has.Janda reports that about 80 percent of salicylanilide 11, compared with 10 percent of the antiparasitic drug, niclosamide (which Janda claims has just entered clinical trials for a COVID-19 treatment), passed into the bloodstream.His laboratory had many modified salicylanilides, but he only used No. Two ways 11 affected pandemic coronavirus infection in pandemic pandemic. It first interfered with the way that the virus stored its genetic material in infected cells. This is called endocytosis. Endocytosis is when the virus forms a lipid-based package around its viral genes. The packet is introduced into the infected cells and then dissolves. This allows the protein-building machinery of the infected cells to read the packet and generate new viruses. No. 11. appears to stop the packet from dissolving.Janda states that the compound's antiviral mechanisms are the key. It prevents the virus material from exiting the endosome and the compound just degrades. This does not permit the creation of new viruses particles as quickly.He adds that because it works inside cells, rather than on viral spikes it is not a concern.AdvertisementJanda states that this mechanism isn't dependent on virus spike protein. Therefore, these new variants aren't going relegated us to finding new molecules like it is with vaccines and antibodies.Additionally, No. Janda states that No. 11 also helped to calm potentially toxic inflammation in the animals. This could be useful for treating acute respiratory distress caused by life-threatening COVID infections. It decreased interleukin 6, which is a signaling protein that contributes to inflammation in advanced stages of COVID-19.We urgently need better medications to combat COVID-19, because highly infectious new variants are driving renewed waves of illness and death worldwide. But Janda says salicylanilide No. Janda says that 11 was invented long before the pandemic.He was a victim of Clostridioides difficile, a nasty bacterial infection that he suffered from about ten years ago. Multi-drug resistant strains of C. difficile are a major reason for drug-resistant diarrheal diseases in hospitals worldwide and among those who use antibiotics. Janda, who was the director of The Worm Institute which focused on parasitic infection, was well-versed in salicylanilides and their antimicrobial properties. His laboratory developed a "library of modified salicylanilides," which were all effective against C. difficile. The collection was later licensed by Sorrento Therapeutics. Salicylanilide 11 was one of them.Janda explains that Salicylanilide 11 was actually put on the back burner in my laboratory to fight C. difficile, because it is not as gut-restricted. "But salicylanilide 11 is a promising therapeutic option for COVID."
