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Source: COVID-19 Natural Cures  Jun 22, 2020  23 days ago
MUST READ! COVID-19 Natural Cures: University Of Alabama Identifies 125 Naturally Occurring Plant Phytochemicals That Could Inhibit COVID-19
MUST READ! COVID-19 Natural Cures: University Of Alabama Identifies 125 Naturally Occurring Plant Phytochemicals That Could Inhibit COVID-19
Source: COVID-19 Natural Cures  Jun 22, 2020  23 days ago
COVID-19 Natural Cures: Researchers from the University of Alabama in Huntsville (UAH) has identified 125 naturally occurring compounds that have a computational potential for efficacy against the COVID-19 virus from the first batch of 50,000 compounds rapidly assessed by a supercomputer.


 
A supercomputer is being utilized to assess the treatment efficacy of naturally occurring compounds against the proteins made by COVID-19. The Baudry Lab Located in UAH's Shelby Center for Science and Technology is searching for potential precursors to drugs that will help combat the global pandemic using the Hewlett Packard Enterprise (HPE) Cray Sentinel supercomputer.
 
The research team is led by molecular biophysicist Dr Jerome Baudry, the Chair from the Department of Biological Sciences.
 
The research findings that have yet to have been peer reviewed are published on a preprint server:  ChemRvix. https://chemrxiv.org/articles/High_Performance_Computing_Prediction_of_Potential_Natural_Product_Inhibitors_of_SARS-CoV-2_Key_Targets/12497693
 
 
Dr Baudry told Thailand Medical News, "We have used supercomputers to predict natural products most likely to bind to three proteins of the SARS-CoV-2 virus. Out of the 50,000 natural products that we have looked at using supercomputers, we find several hundred to be predicted to be potentially binding on the proteins of interest. We further found 125 but there may be more that are particularly interesting because they bind right where we want to, they are not too big, not too small and they have the chemical profiles of pharmaceuticals."
 
He added, "Many of these natural compounds are from relatively common medicinal plants that can be found in the U.S., and many are from more distant plants from Southeast Asia and South America, as well as from some ground and oceanic bacteria strains and fungi."
 
Some of the interesting candidates identified include:
 
-lycorine, found in the red spider lily, Lycoris radiata,
 
-tanshinones, geranylated flavonoids and  tetraorcinol A  found in the coral-associated fungus Aspergilus
 
-rekinamycin, belonging to the kinamycin class of diazofluorene antitumor antibiotics first isolated from the bacteria Streptomyces murayamaensis
 
-cassiarine E (CNP0328498), which is found in the cassia tree Cassia siamea, which is used in traditional medicines in Burma and Thailand.
 
-5,6-dihydro, 5α-chloro-6β-hydroxy-Jaborosalactone  (CNP0252890), one of several jaborosalactones found in  naturally-occurring Withanolide chlorohydrins found in the extracts of species in the genus Jaborosa that have been reported to act as insect anti-feedants. These plants are members of the Solanaceae family and are widely distributed throughout South America.
 
-12,10’- dichloroisoplagiochin  found in Japanese liverwort Herbertus sakuraii.
 
-kadcoccilactone G (CNP0363620) is among several other Kadcoccilactones found in Kadsura coccinea. This genus of climbing plant is found throughout Southeast Asia, where K. coccinea itself is used in cuisine and traditional medicine to treat gastric and duodenal ulcers, gastroenteritis, rheumatism, lumbago, and dysmenorrhea.
 
-aspertryptanthrin B (CNP0110880),  found in several terrestrial and marine species in the genus Aspergillus, but it has not been shown to have biological activity, although many other indole diketopiperazines from this genus have reported cytotoxic effects.
 
-tetraorcinol A, 6- hydroxystaurosporinone (CNP0301743) isolated from the myxomycete Lycogala Epidendrum
 
-asperlicin D (CNP0245001), isolated from the fungus Aspergillus alliaceus, is in the family of mycotoxins known as Asperlicins
 
-deoxy-2,3,3'4',6,7-hexahydro-8-(2,2- dimethyl-2H-benzopyran-6-yl)-5-hydroxy-2,2- dimethyl-2H,6H-benzo[1,2-b:5,4-b']dipyran-6-one49 (CNP0292046) is a flavonoid found in the leaf extract of Artocarpus fulvicortex, a fruiting tree from Indonesia and Malaysia.
 
-apigenin is found in many plants, and is particularly abundant in the flowers of the chamomile plants.
 
-harunganin (CNP0334196), isolated from the dragon's blood tree, Harungana madagascariensis,
 
-beccamarin(CNP0132136) This compound is found in the bark of the ironwood tree, Mesua beccariana, whose extract has been used in traditional medicine to treat fever, renal diseases, poultice and dyspepsia in Malaysia.
 
The researchers said that promising compounds will undergo a computational technique called pharmacophore analysis to find what the chemicals have in common and flag chemical features important for future research.
 
The subsequent next phase for the compounds is in vitro testing by a partner laboratory that will use live virus and live cells. Those chemical molecules found most efficacious will form the basis for future drug research and development processes that include testing for efficacy, tolerance and adverse effects in human trials. That process might also include chemical modifications to make the drug more efficient, better tolerated or both.
 
Dr Baudry added, "Maybe we will need a cocktail of drugs, as is the case in many anti-AIDS treatments. But every drug that ends up surviving this long and winding road of development and testing starts as a hit that binds to a protein. It is this initial event that we are modeling here using supercomputers. Normally it would take a very long time and a lot of money to achieve that, but with the supercomputers we can perform this initial hit discovery step much faster and cheaper. Everything is being accelerated for COVID-19, so the whole process that can take up to a decade may end up being shorter here."
 
The researchers said that In the initial batch, naturally occurring compounds were found that seem likely to bind to two important proteins, COVID-19's papain-like protease, or PLpro, and the main protease, or Mpro. The proteins are enzymes from the virus' genome that are responsible for processing all the virus' proteins in infected cells. Infected cells are forced to manufacture them so that the virus can replicate.
 
Dr Baudry explained, "If we can block these viral proteins from self-assembling and performing their functions inside the cell, we may not have been able to save that one infected cell, but we will prevent the virus from replicating and it will die with that cell, If we find a chemical that 'sticks' in these reactive regions of the proteins, the processing reactions will not be possible anymore and we will stop the infected cells from making and releasing more virus."
 
Most significantly, the third protein of interest is COVID-19's spike protein, which is how the virus attaches itself to a cell to initiate the infection process. This spike protein is present on the surface of the virus and gives the virus its characteristic crown-like (corona in Latin) appearance. It binds to a protein called ACE2 on the cell surface to begin the infection process.
 
Dr Baudry commented, "We are trying to find chemicals that would bind on the surface of the virus' spike protein and prevent it from locking itself with the cell's ACE2."
 
The scientists found in the initial batch modeled, the interactions of 24 compounds interesting in the spike protein, 41 molecules interesting in the main protein and 60 compounds interesting in the PL-pro protein.
 
Dr Baudry added, "We can then have a good idea of what the natural products exhibit that makes them successful in these different proteins, and that is the starting point for screening larger databases of millions of chemicals much faster, helping chemists to synthesize novel molecules down the road, maybe more potent and more selective than the original natural products against these proteins."
 
Thailand Medical News will be providing updates on this research including the next vitro testing phase and the animal testing phase before the research actually proceeds to human clinical trials.
 
For more on COVID-19 Natural Cures, keep on logging to Thailand Medical News.

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