We Apologies For Any Inconveniences As The Site Is Having Some Technical Changes Done With New Modules Coming Soon

Source: COVID-19 Drugs  Aug 07, 2021  6 months ago
BREAKING! Salicylanilides In Anti-Worm Drugs Like Niclosamide Inhibits SARS-CoV-2 Replication And Suppresses Inflammation Causing Cytokines
BREAKING! Salicylanilides In Anti-Worm Drugs Like Niclosamide Inhibits SARS-CoV-2 Replication And Suppresses Inflammation Causing Cytokines
Source: COVID-19 Drugs  Aug 07, 2021  6 months ago
COVID-19 Drugs: A new mouse based vivo study by researchers from the Scripps Research Institute-California along with scientist from the University of Texas and Sorrento Therapeutics Inc.-California have found that salicylanilides which are active pharmaceutical ingredients (APIs) found in drugs used to treat tapeworm infestations demonstrated efficacy in terms of inhibiting the SARS-CoV-2 coronavirus replication and also suppressed cytokines that cause inflammation.

While the world has mobilized to create antiviral vaccines and therapeutics to combat the ongoing COVID-19 pandemic, their long-term efficacy remains in question especially with the emergence of new variants.
The study team wanted to exploit salicylanilides - a class of compounds that has previously shown success against various viruses. A detailed salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections.
The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.
The study findings were published in the peer reviewed journal: ACS Infectious Disease. https://pubs.acs.org/doi/10.1021/acsinfecdis.1c00253
Thailand Medical News had covered about the usage of Niclosamide as potential drug to treat COVID-19 as early as June 2020 based on a Korean research. https://www.thailandmedical.news/news/niclosamide-shows-efficacy-against-covid-19-in-animal-tests-according-to-south-korean-pharmaceutical-giant-daewoong
Thailand Medical News also covered an Indian study on Niclosamide to treat COVID-19 in December 2020. https://www.thailandmedical.news/news/covid-19-drugs-niclosamide-emerging-as-another-potential-repurposed-drug-candidate-to-treat-covid-19-
A Florida based biotech company had also announced its plans to develop a form of niclosamide to treat COVID-19 gastrointestinal infection in early January 2021. https://www.thailandmedical.news/news/pharma-news-azurrx-biopharma-s-proprietary-niclosamide-formulations-to-treat-covid-19-gastrointestinal-infections
Niclosamide, a medications long prescribed to treat tapeworm has inspired a compound that shows two-pronged effectiveness against COVID-19 in laboratory studies, according to the new research.
The bioactive compound, part of a class of molecules called salicylanilides, was designed in the laboratory of Professor Dr Kim Janda, Ph.D., the Ely R. Callaway, Jr. Professor of Chemistry and director of the Worm Institute for Research and Medicine at Scripps Research, in La Jolla, California.

Dr Janda told Thailand Medical News, "It has been known for 10 or 15 years that salicylanilides work against certain viruses. However, they tend to be gut-restricted and can have toxicity issues."
Dr Janda's compound overcomes both issues, in mouse and cell-based tests, acting as both an antiviral and an anti-inflammatory drug-like compound, with properties that auger well for its use in pill form.
The bioactive API - Salicylanilides were first discovered in Germany in the 1950s and used to address worm infections in cattle. Versions including the drug niclosamide are used in animals and humans today to treat tapeworm.
Salicylanilides have also been studied for anti-cancer and antimicrobial properties.
Interestingly the modified salicylanilide compound that Dr Janda created was one of about 60 that he built years ago for another project.
However when the SARS-CoV-2 virus became a global pandemic in early 2020, knowing that they may have antiviral properties, he started screening his old collection, first in cells with collaborators from Sorrento Therapeutics and The University of Texas Medical Branch, and later, after seeing promising results, working with Scripps Research immunologist Dr John Teijaro, Ph.D., who conducted rodent studies.
Importantly one compound stood out. Dubbed simply "No. 11," it differs from the commercial tapeworm medicines in key ways, including its ability to pass beyond the gut and be absorbed into the bloodstream—and without the worrisome toxicity.
Dr Janda added, "Niclosamide is basically digestive-track restricted, and that makes sense, because that's where parasites reside. For that reason, simple drug repurposing for a COVID treatment would be counterintuitive, as you want something that is readily bioavailable, yet does not possess the systemic toxicity that niclosamide has."
The study found that about 80 percent of salicylanilide 11 passed into the bloodstream, compared to about 10 percent of the antiparasitic drug niclosamide, which has recently entered clinical trials as a COVID-19 treatment, Dr Janda said.
The study showed that of the many modified salicylanilides he had built in his laboratory, No. 11 affected pandemic coronavirus infections in two ways. First, it interfered with how the virus deposited its genetic material into infected cells, a process called endocytosis. Endocytosis requires the virus to form a lipid-based packet around viral genes. The packet enters the infected cell and dissolves, so the infected cell's protein-building machinery can read it and churn out new viral copies. No. 11 appears to prevent the packet's dissolution.
Dr Janda stressed, "The compound's antiviral mechanism is the key. It blocks the viral material from getting out of the endosome, and it just gets degraded. This process does not allow new viral particles to be made as readily."
It should also be noted that because it acts inside cells rather than on viral spikes, questions about whether it would work in new variants like Delta and Lambda aren't a concern, he adds.
D Janda explained, "This mechanism is not dependent on the virus spike protein, so these new variants coming up aren't going to relegate us to finding new molecules as is the case with vaccines or antibodies.”
Furthermore, no. 11 helped quiet potentially toxic inflammation in the research animals, Dr Janda says, which could be important for treating acute respiratory distress associated with life-threatening COVID infections. It reduced levels of interleukin 6, a signaling protein which is a key contributor of inflammation typically found in advanced stages of COVID-19.
At present, better and efficient medications against COVID-19 are urgently needed, as highly infectious new variants drive renewed surges of illness and death globally.
Dr Janda added that salicylanilide No. 11 was created long before the pandemic.
D Janda, after fighting an unpleasant bacterial infection called Clostridioides difficile about 10 years ago, saw a clear need for better treatment options.
Alarmingly multi-drug-resistant strains of C. difficile have become a major cause of drug-resistant diarrheal disease outbreaks in health care institutions globally, and among people using antibiotics.
Being a director of the Worm Institute, which focused on parasitic infections, Dr Janda was very familiar with salicylanilides, and knew of their antimicrobial properties.
His research laboratory created a "library" of modified salicylanilides several of which showed strong efficacy against C. difficile, and the collection was subsequently licensed by pharmaceutical firm Sorrento Therapeutics. Among them was salicylanilide 11.
Dr Janda commented, "Salicylanilide 11 actually was placed on the back burner in my laboratory against C. difficile because it's not as gut-restricted as we would like it to be. But salicylanilide 11 has got a lot of really positive things going for it as a potential therapeutic for COVID."
Warning to all ‘Cheap Charlie’ or 'parasitic 'readers, please do not attempt to self-prescribe and consume niclosamide or any anti-worm drugs to treat COVID-19 without consulting a licensed medical doctor first. (Not to say any of them might know anything!) Even worse, please do not attempt to purchase niclosamide meant for veterinary use and consume it unless your a stupid cow!
For the latest on COVID-19 Drugs, keep on logging to Thailand Medical News.


Feb 05, 2020  2 years ago
Source : Thailand Medical news