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Source: COVID-19 Drugs  Aug 15, 2020  2 months ago
BREAKING! COVID-19 Drugs: University Of Chicago Study Identifies Ebselen, A Preexisting Organoselenium Drug As A Potential Candidate For COVID-19 Treatments
BREAKING! COVID-19 Drugs: University Of Chicago Study Identifies Ebselen, A Preexisting Organoselenium Drug As A Potential Candidate For COVID-19 Treatments
Source: COVID-19 Drugs  Aug 15, 2020  2 months ago
COVID-19 Drugs: Researchers from the Pritzker School of Molecular Engineering (PME) at the University of Chicago have identified by using state-of-the-art computer simulations, a potential drug candidate that can be repurposed to treat COVID-19.

The drug Ebselen also called PZ 51, DR3305 orSPI-1005, is a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity. It acts as a mimic of glutathione peroxidase and can also react with peroxynitrite. It is used in experimental aspects for the treatment for reperfusion injury and stroke, hearing loss and tinnitus, and bipolar disorder.
Ebselen is a potent scavenger of hydrogen peroxide as well as hydroperoxides including membrane bound phospholipid and cholesterylester hydroperoxides. Several ebselen analogs have been shown to scavenge hydrogen peroxide in the presence of thiols.
Previous studies preliminarily demonstrated that Ebselen exhibits promising inhibitory activity against COVID-19 in cell-based assays. https://www.nature.com/articles/s41586-020-2223-y
The inhibitory effect was attributed to irreversible inhibition of the main protease via a covalent bond formation with the thiol group of the active center's cysteine (Cys-145).
The new research on Ebselen as a drug candidate by University of Chicago researchers based on its binding potential is currently published on a preprint server but will be published in the journal Science Advances in the next few days as it has already been peer reviewed. https://arxiv.org/abs/2005.09805
Professor Dr Juan de Pablo and his students in the early part of the year had used their molecular modeling expertise to help find a potential treatment against the disease. They were not the only ones. Other groups around the world were beginning to use supercomputers to rapidly screen thousands of existing compounds for potential use against the SARS-CoV-2 virus.
Dr de Pablo explained to Thailand Medical News, "By virtue of the large number of compounds considered in high throughput screens, those calculations must necessarily involve a number of simplifications, and the results must then be evaluated using experiments and more refined calculations."
The study team first focused on finding a weakness in the virus to target. They chose its main protease: Mpro. Mpro is a key coronavirus enzyme that plays a central role in the virus' life cycle. It facilitates the virus' ability to transcribe its RNA and replicate its genome within the host cell.
The pharmaceutical drug that shows promise as a weapon against Mpro was identified and this was Ebselen.
It has been reported that in combination with silver, Ebselen treats five clinically difficult-to-manage antibiotic-resistant Gram-negative bacteria.
Significantly, several clinical trials have prove n its safety for use in humans.
Dr de Pablo and his students set out to develop detailed models of the enzyme and the drug. Using those models and sophisticated supercomputer simulations, they discovered that the small Ebselen molecule is able to decrease Mpro's activity in two different ways.
Dr de Pablo highlighted, "In addition to binding at the catalytic site of the enzyme, Ebselen also binds strongly to a distant site, which interferes with the enzyme's catalytic function by relying on a mechanism in which information is carried from one region of a large molecule to another region far away from it through subtle structural reorganizations."
This new study finding is particularly critical and important because it helped explain Ebselen's potential efficacy as a repurposed drug, and it revealed a new vulnerability in the virus that was previously not known and that could be use useful in developing new therapeutic strategies against COVID-19.
The study team completed their work in just over two months and submitted their manuscript to public research archives in April for others to consider.
The team's discovery of two binding sites looks promising for Ebselen to be a new drug lead for the design and development of new Mpro inhibitors and COVID-19 treatment. Motivated by their findings, de Pablo and his student are quick to point out that much work is yet to be done.
Dr de Pablo added, "The main protease is one of many proteins in the virus that could be targeted with existing, repurposed drugs, and there are thousands of compounds to be considered. We are systematically investigating each of the proteins involved in the virus function and investigating their vulnerabilities and their responses to a wide range of drugs."
Dr de Pablo and his team will soon release a comprehensive study of the RBD/ACE2 complex from the virus and another drug that offers promise to interfere with the binding of the virus to cells.
There are other research teams now planning to test Ebselen’s efficacy against SAR-CoV-2 using vitro and vivo models before initiating any human clinical trials.
However many are skeptical that it would gain recognition or even be accepted as a treatment protocol as there is a concerted effort by pharma giants, certain corrupted governments, social media and even mainstream media platforms in America to ensure that non-patented drug candidates, supplements and herbs do not ever get to be used to treat COVID-19 as they would not be able to profit from it. They would rather that millions die and suffer rather than they lose potential profits. Sadly many common Americans and even Europeans prefer to believe in these entities much to their own detriment.
For more on COVID-19 Drugs keep on logging to Thailand Medical News.


Source: Supplements For COVID-19
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Source : Thailand Medical news
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