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Source: COVID-19 Herbs  Jul 04, 2021  2 years, 8 months, 2 weeks, 1 day, 5 hours, 50 minutes ago

COVID-19 Herbs: Derivative of Sinigrin-A Phytochemical Found In Mustard Seeds Identified As Potent Inhibitor of SARS-CoV-2 3CLPro. Tumeric And Wall Rocket Also Useful For COVID-19

COVID-19 Herbs: Derivative of Sinigrin-A Phytochemical Found In Mustard Seeds Identified As Potent Inhibitor of SARS-CoV-2 3CLPro. Tumeric And Wall Rocket Also Useful For COVID-19
Source: COVID-19 Herbs  Jul 04, 2021  2 years, 8 months, 2 weeks, 1 day, 5 hours, 50 minutes ago
COVID-19 Herbs: A new study by Spanish researchers from the Polytechnic University of Valencia has identified a derivative of the phytochemical called Sinigrin which is extracted from mustard seeds as being a potent inhibitor of SARS-CoV-2 3CLPro activity, hence a potential antiviral for treating the COVID-19 disease.

Sinigrin is a glucosinolate that belongs to the family of glucosides found in some plants of the family Brassicaceae such as Brussels sprouts, broccoli, and the seeds of black mustard (Brassica nigra). Whenever sinigrin-containing plant tissue is crushed or otherwise damaged, the enzyme myrosinase degrades sinigrin to a mustard oil (allyl isothiocyanate), which is responsible for the pungent taste of mustard and horseradish. Seeds of white mustard, Sinapis alba, will give a much less pungent mustard because this species contains a different glucosinolate, sinalbin.
 
The chemical name of sinigrin is allylglucosinolate or 2-propenylglucosinolate. Singrin is also known to be allelopathic.
 
The resultant hydrolysis product of sinigrin called allyl isothiocyanate exhibits potent inhibitory properties against SARS-CoV-2 3CLPro activity.
 
Allyl isothiocyanate (AITC) is the organosulfur compound with the formula CH2CHCH2NCS. This colorless oil is responsible for the pungent taste of mustard, radish, horseradish, and wasabi. Studies have also shown Allyl isothiocyanate to have cancer chemopreventive properties.
 
The study also identified 17 other plant products commonly used in current and traditional cuisine that have previously shown promise as inhibitors of a coronavirus protein called chymotrypsin-like protease (3CLPro).Some of these included wall rocket and also turmeric.
 
Critically, antiviral treatments inhibiting SARS-CoV-2 replication may represent a strategy complementary to vaccination to fight the ongoing COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CLPro) could contribute to reducing or suppressing SARS-CoV-2 replication.
 
Utilizing a detailed targeted approach, the study identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CLPro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro activity using a quenched fluorescence resonance energy transfer (FRET) assay.
 
Phytochemical extracts from turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides) at 500 µg mL−1 displayed significant inhibition of the 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively.
 
Utilizing different extract concentrations, an IC50 value of 15.74 µg mL−1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibit ing the 3CLPro activity.
 
However Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CLPro inhibitory activity but its hydrolysis product allyl isothiocyanate had an IC50 value of 41.43 µg mL−1.
 
The study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.
 
The study findings were published in the peer reviewed journal: Foods.
https://www.mdpi.com/2304-8158/10/7/1503/htm
 
3CLPro is the viral protein required for successful replication of the SARS-CoV-2 coronabvirus-the pathogen responsible for the ongoing COVID-19 pandemic.
 
The study analysis revealed that extracts of turmeric, mustard seed, and wall rocket exhibited significant inhibition of SARS-CoV-2 3CLPro activity. The study also revealed that a derivative of sinigrin, which is found in mustard seeds, was also a potent inhibitor of SARS-CoV-2 3CLPro activity.
 
Corresponding author Dr Carla Guijarro-Real from the Polytechnic University Of Valencia told Thailand Medical News, “Testing plant extracts can be considered a first approach in the search for natural compounds with antiviral activity, or even represent a basis for the development of prophylactic or therapeutic plant extracts against COVID-19.”
 
She added, “In addition, given the proven safety for human consumption of the plants from which extracts are obtained, their potential use against COVID-19 might be immediate and easily accessible.”
 
Ever since the SARS-CoV-2 outbreak began in late December 2019, intense research efforts have led to the development and emergency use authorization of several COVID-19 vaccines that are now being rolled out on a mass scale globally.
 
Dr Guijarro-Real stressed, “Several of the first-generation vaccines already in use in vaccination campaigns have shown high levels of efficacy, albeit the level of protection is not complete and seems to be variant-dependent. Furthermore, vaccines are in short supply in some regions, and in many countries, vaccination against SARS-CoV-2 is neither compulsory nor indicated for some specific groups, such as children or people with certain health conditions.”
 
She further added, “Obtaining effective treatments against SARS-CoV-2 is urgently needed because, in combination with vaccines, they may become a first-line therapy not only for current SARS-CoV-2 variants but also for new ones.”

Past studies has shown that the SARS-CoV-2 protein 3CLPro is required for the proteolytic processing of viral polyproteins during the maturation step and is therefore essential for successful viral replication.
 
Dr Guijarro-Real further added, “The fundamental role of the 3CLPro in viral replication makes this enzyme an attractive target for the development of drugs inhibiting the virus replication.”
 
Numerous recent emerging studies have identified various natural compounds that may have potential antiviral activity against SARS-CoV-2 and have also identified plant-based extracts such as glucosinolates, flavonoids, and other phenolic compounds as likely inhibitors of 3CLPro.
 
With a reference on these previous studies, the study team used a targeted approach to identify 17 plant products as potential inhibitors of 3CLPro activity.
 
Dr Guijarro-Real said, “The materials selected constitute common food products in many cultures and are of easy access or, alternatively, grow profusely in many regions and are included in traditional cuisines.”
 
Some of these identified plant products included citrus fruit peels, lemon, lime, grapefruit, celery, parsley, dill, sweet chamomile, dried oregano, red onion, turmeric, aloe vera, brown mustard seeds, horseradish, commercial wasabi powder, wall rocket, and wild rucola.
 
The study team evaluated methanolic extracts in vitro for inhibition of SARS-CoV-2 3CLPro activity using a quenched fluorescence resonance energy transfer (FRET) assay.
 
The detailed inhibition of SARS-CoV-2 3CLPro activity was tested at a final extract concentration of 500 µg mL−1. The lime peel and chamomile extracts produced signal interferences and were therefore excluded from the analysis.
 
The study found that seven of the plant products exhibited low inhibitory capacity against 3CLPro, for which the average residual activity was more than 70%. These products included extracts of grapefruit, lemon, orange fruit peel, red onion, celery stalk, horseradish, and dill.
 
Whereas five other materials exhibited an intermediate inhibitory capacity (35–55%), including extracts of celery leaves, parsley, oregano herbs, aloe vera leaves, and wasabi powder.
 
However three extracts exhibited high inhibitory capacity, including wall rocket, mustard seeds, and turmeric rhizomes, which resulted in residual 3CLPro activity of 14.9%, 9.4%, and 0.0%, respectively.
 
Dr Guijarro-Real added, “The turmeric extracts were, in fact, the most effective among all the plant-based extracts evaluated in the inhibitory activity.”

But when the study team tested commercial curcumin, (curcumin is the principal curcuminoid in turmeric) SARS-CoV-2 3CLPro activity was no longer fully inhibited, suggesting that other components in the turmeric extract must contribute to the inhibition.
 
Dr Guijarro-Real explained, “The inhibitor capacity of turmeric extracts might be the result of a synergistic activity of several compounds. Overall, our results indicate that extracts of turmeric are a strong candidate for being tested for inhibition of the in vivo replication of SARS-CoV-2.”
 
The research also revealed that a derivative of sinigrin ie allyl isothiocyanate potently inhibited  3CLPro activity. Sinigrin is a major glucosinolate present in mustard seed and wall rocket.
 
The study team says the results suggest that this sinigrin derivative is also a good candidate molecule for in vivo testing against 3CLPro activity.
 
Dr Guijarro-Real cautioned, “However, the high cytotoxicity of allyl isothiocyanate may preclude its practical use, which would depend on the concentration required. Further analysis of the methanolic extracts for mustard and wall rocket would increase the knowledge regarding the concentration at which these compounds are found, and the possible presence of other metabolites also exerting potential inhibitory activities.”
 
The study team did however advise that eating diets rich in these plants might be useful during this current pandemic while actual therapeutics based on the extracts and derivatives of these plants are being researched and developed.
 
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For the latest on COVID-19 Herbs, keep on logging to Thailand Medical News.
 

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