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Chemical Compounds in Foods Can Inhibit a Key SARS-CoV-2 Enzyme

Photo of muscadine grapes on the vine.
Chemical compounds in muscadine grapes effectively inhibit an important SARS-CoV-2 protease. Photo courtesy of De-Yu Xie, NC State University.

For Immediate Release

De-Yu Xie

Chemical compounds in foods or beverages like green tea, muscadine grapes and dark chocolate can bind to and block the function of a particular enzyme, or protease, in the SARS-CoV-2 virus, according to a new study by plant biologists at North Carolina State University.

Proteases are important to the health and viability of cells and viruses, says De-Yu Xie, professor of plant and microbial biology at NC State and the corresponding author of the study. If proteases are inhibited, cells cannot perform many important functions – like replication, for example.

“One of our lab’s focuses is to find nutraceuticals in food or medicinal plants that inhibit either how a virus attaches to human cells or the propagation of a virus in human cells,” Xie said.

In the study, the NC State researchers performed both computer simulations and lab studies showing how the so-called “main protease” (Mpro) in the SARS-CoV-2 virus reacted when confronted with a number of different plant chemical compounds already known for their potent anti-inflammatory and antioxidant properties.

“Mpro in SARS-CoV-2 is required for the virus to replicate and assemble itself,” Xie said. “If we can inhibit or deactivate this protease, the virus will die.”

Photo of green tea.
Green tea has chemical compounds effectively blocked an important SARS-CoV-2 enzyme. Photo courtesy of De-Yu Xie, NC State University.

Computer simulations showed that the studied chemical compounds from green tea, two varieties of muscadine grapes, cacao powder and dark chocolate were able to bind to different portions of Mpro.

“Mpro has a portion that is like a ‘pocket’ that was ‘filled’ by the chemical compounds,” Xie said. “When this pocket was filled, the protease lost its important function.”

In vitro lab experiments completed by Yue Zhu, an NC State Ph.D. student in Xie’s lab, showed similar results. The chemical compounds in green tea and muscadine grapes were very successful at inhibiting Mpro’s function; chemical compounds in cacao powder and dark chocolate reduced Mpro activity by about half.

“Green tea has five tested chemical compounds that bind to different sites in the pocket on Mpro, essentially overwhelming it to inhibit its function,” Xie said. “Muscadine grapes contain these inhibitory chemicals in their skins and seeds. Plants use these compounds to protect themselves, so it is not surprising that plant leaves and skins contain these beneficial compounds.”

The paper appears in Frontiers in Plant Science. Zhu is the paper’s first author. The research was supported by the U.S. Department of Agriculture.


Note to editors: An abstract of the paper follows.

Docking characterization and in vitro inhibitory activity of flavan-3-ols and dimeric proanthocyanidins against the main protease activity of SARS-Cov-2

Authors: Yue Zhu and De-Yu Xie, NC State University

Published: Nov. 30, 2020 in Frontiers in Plant Science

DOI: 10.3389/fpls.2020.601316

Abstract: We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. The resulting data predicted that all 12 metabolites could bind to Mpro. The affinity scores of PA2 and PB2 were predicted to be ?9.2, followed by ECG, GCG, EGCG, and CAG, ?8.3 to ?8.7, and then six flavan-3-ol aglycones, ?7.0 to ?7.7. Docking characterization predicted that these compounds bound to three or four subsites (S1, S1?, S2, and S4) in the binding pocket of Mpro via different spatial ways and various formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the Mpro activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29?M, respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation, and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.

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  1. Grapes are good. Red grapes are better (resveratrol). Muscadines five times better. Eat the skin, seeds and pulp is even mo’betta!

  2. The seeds have the highest concentration of beneficial compounds, but the entire grape is also good. How much? I don’t think you can overdose on muscadine grapes, unless you consider the sugar content as bad for you. So, more is better.

  3. Excellent and logical. Potent antioxidants and flavonoids in foods seem to offer natural protections against a variety of health hazards. Dr. Angelena Guskova was probably the most competent medical practitioner in the world for treating radiation sickness at Hospital No. 6 in Moscow when Chernobyl exploded. She treated her patients with nutrition, vitamins, blood transfusions, antibiotics, chelating agents and gamma globulin to build their immune systems.

  4. If these plant compounds are ingested orally, it seems like they would still be able to reduce the viral load in the oral, tracheal and digestive areas before they’re changed by the digestive process. Maybe even remain active during the digestive and eliminative processes and in the blood stream. I’ll try it.

  5. many of us will be pleased with the news about dark chocolate, in particular… but what about the processed sugar that’s usually present in most chocolate concoctions? Does that have an effect for good or ill on the virus?

  6. Interesantísimo y de enorme importancia cultural, este artículo acerca de la capacidad que tienen algunos portentosos alimentos como las uvas muscadine y el cacao: el auténtico chocolate oscuro, para desactivar la letalidad de las M-proteínas que se estructuran y multiplican virus como el SARS o covid…. ¡Gracias por compartir tan interesante documento, que confirma lo que por herencia cultural han venido practicando durante siglos y continúan desarrollando algunos pueblos mayas de los Altos de Chiapas para prevenir y evitar contagios de Covid…. Aunque todavía es temprano para proclamarlo, la profilaxis o medicina natural, cuyo principio esencial es la buena y sana nutrición, a base de alimentación vegetal y la prevención de enfermedades por medio de efectivas prácticas herbolarias, que refuerzan las defensas naturales , han comprobado su eficacia para evitar los peligrosos contagios que caracterizan a la actual pandemia y contingencia…
    Las uvas, y más aún las uvas muscadine, que inhiben y pueden desactivar La M-pro del SARS 19, nos recuerdan. Por los aspectos gregarios de sus frutos y los enredos de sus hojas y rizomas, que tal vez en verdad hubo un Ar, un Edén o Paraíso, no sólo en lo que ahora se conoce como el “Viejo Mundo”, sino también en este Nuevo Mundo, como en la región del Xokonoxko, el Soconusco, que durante milenios fue pródigo en el prodigioso árbol de Kakaw, el Cacao, del que ahora se sabe que es también un poderoso desactivador de la M-Pro que hace mortífero al COVID, además de ser un SuperAlimento con una serie de propiedades profilácticas y curativas… Hubo tiempos en que los homo “sapiens”, como soberbiamente nos hemos autodesignado los depredadores seres humanos, disfrutamos en los 5 continentes de verdaderos Paraísos providentes y pletóricos de vergeles que se representaron como míticos “Cuernos de la Abundancia” y “Fuentes de Eterna Juventud”, de los que no hicimosnada mejor que depredarlos, menospreciarlos y desperdiciarlos…

    1. Y que piensas del proceso de digestion, va a effectar la eficiencia contra del enzima?

      Ya Febrero de 2021, y no hay noticia de esto

  7. What other plant compounds were included in this test?

    Were the plant compounds applied directly to the virus? Or were the plant compounds broken down similar to how enzymes in our stomach would break them down first before applying to the virus?

    How was the test conducted?

  8. I would avoid green tea because of several chemicals in it such as caffeine, theobromine, tannins just to name a few. Dark chocolate has some of the same chemicals, but are a different isomer…no tannins. Tannins are why British teeth look bad. If they do that to teeth, think of what else they can do to your body.

  9. How much green tea, grapes, cocoa, dark chocolate would need to be consumed to achieve the desired results? How does the green tea need to be consumed, drinking, supplement,etc. what are Muscadine grapes and is it required for the seeds to be consumed to get the desired effect?

      1. Xie said. “Muscadine grapes contain these inhibitory chemicals in their skins and seeds. Plants use these compounds to protect themselves, so it is not surprising that plant leaves and skins contain these beneficial compounds.”

  10. What are the varieties of the two muscadines? Does anyone know?

    I normally discard the hulls and seeds in the fermentation bag after making wine but I wonder if this could be used in a powder form and taken orally with food as a preventative medicine? Does anyone know how to contact the authors?

    1. You will find the authors contact info at the top of this article.(Even a telephone #)I am also wondering about the variety of muscadines as I have 2 planed but both are white grapes. Was able to find some juice so am hoping it is right kind. Please post variety if you find out.

  11. Thank you!!! Wonderful research.
    Encouraging news…should be newspaper headlines…
    perhaps could help enlighten science disbelievers.

  12. That is great news!!! Thanks so much for sharing your breakthrough with the world… Its nice to know Mother Nature can defeat this man-made virus.

  13. What about other grape types, especially those used in red wine? Great news, thanks for doing the research

  14. Thanks to both researchers for publishing this story. It’s new and important info to me. And thanks to NCSU and USDA for supporting the work, and contributing to Public Health in the USA and the world..

  15. A lot of effects occur in-vitro that aren’t replicated within the human body. If a nasal spray/slow-release lozenge is developed with the food compounds used in the study, those enzymes could then come close to making direct contact with the virus and possibly render results that the NCSU scientist speculates. However, once foods are quickly ingested and go through the digestive process, enzymes and other components aren’t able to affect virus cells directly and in the same concentrations as are used in a lab setting when placed in direct contact.

    1. I wondered if their research was with green tea, dark chocolate, etc., after it was ingested & digested or if it was applied directly.
      That would make a difference.