COVID-19 Therapeutics: Computational Screenings Show A Variety Of Natural Phytochemicals Could Have Efficacy Against SARS-CoV-2 Including EGCG From Green Tea

Source: COVID-10 Therapeutics May 11, 2020 4 years, 6 months, 6 days, 9 hours, 30 minutes ago

COVID-19 Therapeutics: In many drug repurposing and potential therapeutics studies, researchers first use computational screening platforms that involves models of the SARS-CoV-2 coronavirus in detail especially the binding sites of the spike proteins and to match molecular models of existing drugs, supplements, phytochemicals etc to see which have a greater affinity to bind to these sites, hence rendering the virus inactive or unable to bind to the human host cells and replicate.

Many models are already available online for researchers to access and they show in extreme detail the “docking sites” or sites on the spike proteins that binds to human host cells. There are numerous of such docking sites with unique molecular properties and researchers using computational programmes have to identify therapeutic molecules that can effectively dock at those sites to render the SARS-CoV-2 inactive. Upon finding such candidates, typically the next step is to conduct vitro studies, animal studies before proceeding to human clinical trials.

In one interesting study conducted by Indian researchers from Era University in Lucknow, the team studied 18 natural dietary phytochemicals, nutraceuticals such as alpha-lipoic acid and also chloroquine and remdesivir interactions with the molecular docking sites of 7 identified spike proteins found on the surface of the SARS-CoV-2 coronavirus. https://www.researchsquare.com/article/rs-19560/v1

In the study the 18 dietary molecules studied were epigallocatechin gallate (EGCG), piperine, apigenin, curcumin, gingerol-[6], beta glucan, resveratrol, myricetin, quercetin, genistein, diadzein, alliin, allicin, sulphoraphane, phycocyanobillin, ferulic acid and alpha lipoic acid.

Some of these promising dietary molecules could be developed as therapeutic agents in the prevention and treatment of current COVID–19 disease. In previous studies, numerous dietary molecules such as curcumin, savinin and betulinic acid have been found to show inhibition of 2003 SARS-CoV in the range of 3–10 μM concentrations https://www.researchgate.net/publication/326915905_Discovering_Health_Benefits_of_Phytochemicals_with_Integrated_Analysis_of_the_Molecular_Network_Chemical_Properties_and_Ethnopharmacological_Evidence or https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115900/

Another study also showed that, kaempferol, quercetin, luteolin–7-glucoside, demethoxycurcumin, naringenin, apigenin–7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate have been identified as significant anti-SARS-CoV agents with the help of also molecular docking studies. https://tmu.pure.elsevier.com/en/publications/specific-plant-terpenoids-and-lignoids-possess-potent-antiviral-a

Among these dietary molecules, epigallocatechin gallate (EGCG) which is found abundantly in green tea, was found as most active agent against COVID–19.

Please help support this website by kindly making a donation to sustain this website and also all in all our initiatives to propel further research: https://www.thailandmedical.news/p/sponsorship

EGCG showed highest binding affinity (–9.30kcal/mole) and lowest inhibition constant (0.152µM) for the 6y2e spike protein. Moreover, EGCG exhibited a strong molecular interaction with 6vw1 which is an important target of this new coronavirus. It showed highest binding affinity and lowest inhibition constant with –8.66 kcal/mole and 0.152µM values respectively. Further, EGCG displayed excellent interactions with 6vww wherein it showed highest binding affinity (–8.38 kcal/mole) with lowest inhibition constant at 0.724 µM concentration. Additionally, EGCG also exhibited good molecular interactions with SARS-CoV–2 proteins 6lu7, 6lvn, 6lxt, and 6vsb with the values of binding energies and inhibition constant as –6.99, –4.90, –7.57, –7.26 kcal/mole and 7.57, 255.95, 2.84, 4.75 µM concentrations. The computed activity of EGCG was found to be higher than that of both reference drugs, Remdesivir and Chloroquine.

Table : Molecular docking values of phytochemicals against target protein macromolecules

Phytochemicals		Targets Proteins; binding energy in kcal/mole (inhibition constant in µM)
		6lu7	6lvn	6lxt	6vsb	6vw1	6vww	6y2e
1	EGCG	-6.99 (7.57)	-4.90 (255.95)	-7.57 (2.84)	-7.26 (4.75)	-8.66 (0.451)	-8.38 (0.724)	-9.30 (0.152)
2	Curcumin	-6.04 (37.57)	-4.73 (340.89)	-5.50 (92.90)	-5.05 (197.96)	-7.13 (5.91)	-7.37 (3.96)	-7.39 (3.83)
3	Apigenin	-5.96 (43.03)	-3.71 (1.9x10-5)	-5.13 (1.74x10-5)	-5.98 (4.1x10-5)	-6.02 (38.69)	-6.48 (17.86)	-7.05 (6.76)
4	Beta Glucan	-5.96 (42.79)	-4.16 (889.95)	-5.06 (195.39)	-3.20 (4.4x10-5)	-6.44 (19.09)	-6.72 (11.86)	-7.05 (6.83)
5	Myricetin	-5.38 (114.10)	-3.70 (1.96x10-5)	-5.74 (62.01)	-6.14 (31.32)	-6.50 (17.16)	-6.57 (15.20)	-7.15 (5.79)
6	Quercetin	-5.29 (132.27)	-3.68 (2.02x10-5)	-5.73 (63.52)	-6.14 (31.32)	-6.59 (14.73)	-6.53 (16.36)	-6.77 (10.86)
7	Piperine	-5.16 (165.72)	-4.08 (1.02x10-5)	-5.40 (109.87)	-6.05 (36.85)	-5.64 (73.80)	-6.18 (29.44)	-6.40 (20.37)
8	Genistein	-5.03 (204.91)	-3.97 (1.24x10-5)	-5.68 (69.09)	-6.54 (16.04)	-6.35 (22.18)	-6.73 (11.70 )	-6.80 (10.32)
9	Diadzein	-4.86 (275.53)	-3.72 (1.89x10-5)	-5.21 (151.77)	-6.16 (30.34)	-5.96 (42.54)	-6.43 (19.50)	-6.05 (36.86)
10	Ferulic acid	-4.76 (322.26)	-2.79 (9.00x10-5)	-3.75 (1.80 x10-5)	-5.44 (103.05)	-3.74 (1.8x10-5)	-3.90 (1.3 x10-5)	-4.71 (355.68)
11	Alliin	-4.66 (385.74)	-3.90 (1.37x10-5)	-5.02 (210.26)	-4.57 (447.67)	-5.15 (168.32)	-4.07 (1.0 x10-5)	-5.68 (68.09)
12	Lipoic acid	-4.58 (439.80)	-1.90 (40.6x10-5)	-3.25 (4.16x10-5)	-4.93 (243.60)	-2.73 (9.9x10-5)	-3.38 (3.3 x10-5)	-3.59 (2.3x10-5)
13	Resveratrol	-4.20 (832.91)	-3.58 (2.38x10-5)	-4.32 (685.04)	-5.57 (82.09)	-5.26 (138.32)	-5.57 (83.02)	-5.54 (86.98)
14	Glucosamine	-4.06 (1.06x10-5)	-3.59 (2.32x10-5)	-5.26 (138.93)	-4.89 (262.36)	-6.77 (10.89)	-4.18 (862.43)	-4.70 (359.49)
15	Gingerol-[6]	-4.00 (1.16)	-2.23 (23.38)	-3.08 (50.56)	-4.46 (537.58)	-4.60 (425.87)	-4.57 (449.30)	-5.30 (130.87)
16	Sulforaphane	-3.74 (1.81x10-5)	-2.25 (22.3x10-5)	-3.11 (5.22x10-5)	-3.43 (3.0x10-5)	-3.46 (2.9x10-5)	-3.21 (4.4x10-5)	-4.21 (815.35)
17	Allicin	-3.46 (2.89x10-5)	-2.09 (29.4x10-5)	-3.20 (4.49x10-5)	-3.46 (2.92)	-3.07 (5.6x10-5)	-3.14 (5.0x10-5)	-3.63 (2.1x10-5)
18	PCB	+0.16, (Nil)	-3.12 (5.14x10-5)	-4.63 (4.05x10-5)	+11.3 (Nil)	-3.59 (2.3x10-5)	-6.14 (3.1x10-5)	-5.15 (1.6x10-5)
19	Remdesvir	-2.47 (15.4x10-5)	-2.68 (10.7x10-5)	-4.84 (281.48)	-4.27 (745.64)	-5.27 (136.97)	-5.10 (183.96)	-5.47 (97.23)
20	Chloroquine	-3.62 (2.2x10-5)	-3.26 (4.0x10-5)	-4.35 (651.5)	-4.79 (309.3)	-6.41 (19.9)	-4.85 (277.5)	-6.10 (33.5)

6lu7: Main protease of covid-19; 6lvn: Structure of the 2019-nCoV-HR2 Domain; 6lxt: Structure of post fusion core of 2019-nCoV S2 subunit; 6vsb: Prefusion 2019-nCoV spike glycoprotein; 6vw1: Structure of 2019-nCoV chimeric receptor-binding domain complexed with its receptor human ACE2; 6vww: Crystal structure of NSP15 endoribonuclease from SARS CoV-2; 6y2e: Crystal structure of the free enzyme of the SARS-CoV-2 (2019-nCoV) main protease. Remdesvir and Chloroquine are used as standard drugs to compare our results; EGCG: Epigallocatechin gallate; PCB: Phycocyanobillin

Though the pre-print study was published on 27^th March 2020, and has yet to be peer-reviewed, there was intense lobbying by huge pharmaceutical corporations to not focus any research on phytochemical or dietary supplements that were not patented as it would not benefit them and might even affect the business prospects of other drugs that they instead wanted to peddle for profitability gains.

Even various international news media refused to cover on this study as many are directly or indirectly controlled by government authorities and pharmaceutical corporations.

It is also interesting that many of these phytochemicals and dietary molecules were found in Traditional Chinese Medicine formulations that were used in China to treat COVID-19 patients.

It is hope that more of the larger Western research entities would pay more attention to this research findings to further conduct more detailed studies and clinical trials to test the efficacy of this common, cheaper and harmless phytochemicals and nutraceuticals to treat COVID-19 rather than expensive toxic drugs being peddled by the greedy pharmaceutical giants and corrupted government authorities in the US, Europe and even China.

Thailand Medical News however warns that readers should not simply go out and start purchasing any supplements and start consuming them without consulting a doctor first and also till further studies emerge to ascertain their efficacy. Also simply taking some of these dietary supplements could create a false sense of wellbeing that could be dangerous to the person and also others. Also beware of any supplement companies making any false claims of any products that can treat or cure COVID-19 till there are real substantial studies.

For more on COVID-19 Therapeutics and drug research, keep logging to Thailand Medical News.

Please help support this website by kindly making a donation to sustain this website and also all in all our initiatives to propel further research: https://www.thailandmedical.news/p/sponsorship