An Austrian Biotech And German Scientists Explore Using A Natural Lectin From Bread Wheat Called Wheat Germ Agglutinin (WGA) To Treat COVID-19
Researchers from Friedrich-Alexander University Erlangen-Nürnberg-Germany and the University Hospital Tübingen-Germany along with experts from Marinomed Biotech AG-Austria are exploring the antiviral properties of a natural lectin from bread wheat (Triticum vulgaris) called Wheat Germ Agglutinin
(WGA) to treat COVID-19.
Their study findings showed that the Wheat Germ Agglutinin (WGA) demonstrated antiviral properties not only against the original wildtype SARS-CoV-2 coronavirus but also against the Alpha and Beta variants as well.
To date several natural compounds have shown potential as antiviral substances and have the advantages of broad availabilities and large therapeutic windows.
The Austrian and German study team report that lectin from Triticum vulgaris (Wheat Germ Agglutinin) displays antiviral activity against SARS-CoV-2 and its major Variants of Concern (VoC), Alpha and Beta.
The study findings showed that in Vero B4 cells, WGA potently inhibits SARS-CoV-2 infection with an IC50 of <10 ng/mL. WGA is effective upon preincubation with the virus or when added during infection.
Pull-down assays demonstrate direct binding of WGA to SARS-CoV-2, further strengthening the hypothesis that inhibition of viral entry by neutralizing free virions might be the mode of action behind its antiviral effect. Furthermore, WGA exhibits antiviral activity against human coronavirus OC43, but not against other non-coronaviruses causing respiratory tract infections.
The study findings also showed that WGA inhibits infection of the lung cell line Calu-3 with wild type and VoC viruses with comparable IC50 values.
The study findings indicate that topical administration of WGA might be effective for prophylaxis or treatment of SARS-CoV-2 infections.
The study findings were published in the peer reviewed International Journal of Molecular Sciences. https://www.mdpi.com/1422-0067/22/19/10205/htm
The dire need for effective antiviral drugs against the SARS-CoV-2 coronavirus cannot be denied despite the mass global vaccination program underway.
At present several natural compounds are under study for their antiviral potential. Many natural substances have been studied for their antiviral activity against a variety of viruses. Since the coronavirus 2019 (COVID-19) pandemic, the focus has been testing natural substances for their potential antiviral effects against SARS-CoV-2. To that effect, many naturally derived compounds are undergoing clinical studies.
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides.
Lectins, a class of naturally derived compounds have the potential to bind viral envelope glycoproteins and exhibit antiviral activity against several viruses.
The lectin from Common Wheat or Bread Wheat (Triticum vulgaris) is also known as Wheat Germ Agglutinin (WGA). It demonstrates a
ntifungal activity. It has applications in cell imaging and the potential for improved drug delivery.
However, till now, there were no previous studies are testing its antiviral activity against SARS-CoV-2.
The study team investigated the anti-SARS-CoV-2 potential of WGA in vitro.
Simulated infection experiments were performed to examine the antiviral activity of WGA against SARS-CoV-2. Vero B4 cells were infected with a Wuhan type SARS-CoV-2 isolated from a patient. These infected cells were then treated with different concentrations of WGA.
The study findings showed that SARS-CoV-2 replication was reduced due to WGA treatment. Moreover, this reduction was dose-dependent. This was the first evidence that showed that WGA demonstrates antiviral activity.
As lectins in general, are viral entry inhibitors, a similar mode of inhibition was expected with WGA.
In order to test this, the study team preincubated the SARS-CoV-2 patient isolates with different concentrations of WGA and then infected Vero B4 cells.
It was found that WGA completely blocked the viral infection of cells, hence acting as an entry inhibitor. WGA may physically interact with the virus and neutralize it. Direct binding of WGA to SARS-CoV-2 viral particles was confirmed through pull-down assays.
WGA has been shown to exert cytotoxic activity on different cancer cell lines, such as pancreatic, liver, bone, and skin cancer cells according to past studies. It exhibited time- and dose-dependent cytotoxicity towards acute myeloid leukemia cells in low doses, while no effect on normal cells was observed.
Importantly even if WGA demonstrates antiviral activity, it will have no therapeutic potential if it is toxic to host cells. Hence the study team performed toxicity assays in all cell lines used for the study.
WGA showed no cytotoxic effect. The toxic dose varied among the tested cell lines, but there was still a broad therapeutic window of several log stages.
Importantly the antiviral activity of WGA was also tested against two SARS-CoV-2 variants ie Alpha and Beta. Cell infection assays were done with Calu-3 cells. WGA inhibited infection of cells by the Alpha and Beta variants, but at different concentrations.
The study team also tested the antiviral activity of WGA against human coronavirus (hCoV) OC43, another member of the Betacoronavirus family. And also Rhinovirus serotype 1A (hRV1a), human Rhinovirus serotype 8 (hRV8), and Coxsackievirus A10.
WGA exhibited moderate antiviral activity against endemic hCoV OC43. Conversely, WGA did not inhibit binding and replication of other virus families, causing upper respiratory tract infections.
The exploring of natural substances rather than synthetic drugs for therapeutic potential is advantageous because natural compounds have better toxicological profiles with larger therapeutic windows, fewer side effects, and a faster admission process.
Many natural substances have demonstrated their beneficial effects against many diseases, including metabolic disorders or cancer. They have also shown promising results against different viruses, including SARS-CoV and Middle East respiratory syndrome virus (MERS-CoV).
As the study findings showed that WGA reduced infection of SARS-CoV-2, it can be postulated that it could prevent the transition of a mild COVID-19 infection to a severe stage of the disease.
The study findings pave the way for future preclinical research testing the prophylactic and therapeutic potential of WGA. Since its mode of action is exerted via binding the viral particle, WGA could be an ideal candidate for a nasal or throat spray.
The study findings also suggest that WGA could provide beneficial prophylactic and therapeutic effects. Due to its low cytotoxicity, the broad therapeutic window, and the rich availability in nature, it would be an easily distributable agent in the current pandemic and future pandemics.
Researchers wanting to also conduct further studies or clinical trials on WGA can contact Thailand Medical News directly as our sister company-Northern Thai Herbs will be giving away complimentary stocks of WGA pending certain conditions. Kindly contact us directly.
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