Can plant phytonutrients grown in a controlled environment help people recover from Covid-19 and long Covid?

“First, do no harm” Hippocrates 

Covid-19 effects are the most well known in the world. More than a year on from the start of the pandemic and despite the roll out of effective vaccines in richer countries we still have a limited drug arsenal with worldwide coverage to make life easier for those most at risk. According to physicians at the Mayo clinic, the FDA have approved the antiviral drug Remdesivir and emergency use of the anti-inflammatory drug Baricitinib for use in patients hospitalised with COVID-19. In the UK Dexamethasone, an anti-inflammatory corticosteroids is authorised for use in severe cases. Studies found this drug reduces the risk of death by about 30% for people on ventilators and by 20% for people who need supplemental oxygen. But Dexamethasone and other corticosteroids may actually be harmful if given for less severe COVID-19 infections so it is reserved only for the critically ill. Clinical studies in the UK this year showed an additional benefit from the combination of two drugs used for rheumatoid arthritis, Tocilizumab and Sarilumab, which reduced the risk of mortality in ICU patients by 24%.  

Researchers across the world are examining the effects of anti-inflammatory drugs and other immunotherapies to suppress the virus. Controversial anti-malarial drugs were initially thought to control the virus but were quickly withdrawn by the FDA when data analysis showed that Hydroxychloroquine and Chloroquine were NOT effective for treating COVID-19 and can lead to serious heart problems. 

Epidemiologists writing in the journal Nature suggest Coronavirus is going to stay with us for some time. Then there’s the effect it leaves behind on our bodies, a new disease called Long Covid or as some in the US are calling it Long Haul Covid. Long covid is now defined by time post infection and acute long covid lasts 3 weeks whereas chronic long covid is ongoing for more than 12 weeks. The effects of long covid are wide ranging with some not even aware they have it, and symptoms include diarrhoea, nausea, vomiting and gastrointestinal pain. For those that recover from serious illness the effects can be life changing and far reaching including muscle loss, organ failure, reduced lung capacity, brain fog and even depression. 

Researchers are still learning how an infection with SARS-CoV-2 affects different parts of the body so new medicines can be developed. Although there is hope on the horizon with new antiviral drugs like TEMPOL and others in development we must remember the pathways of this disease are complex and still emerging. 

With this backdrop in mind we hope medicinal plant derived products that selectively block the ACE2 receptor may provide alternative ways to treat SARS-CoV-2. This blog is designed to be of interest to people with an interest in foods that can have a medicinal effect, growers who aim to produce unique medicinal crops and for scientists interested in the pharmaceutical properties of plants. 

Mechanism of cell entry and replication causing inflammation

We need to understand how the virus affects our bodies to know how to prevent dangerous physiological changes. Studies show the SARS-CoV-2 virus enters via epithelial and endothelial cells on the inner surface of blood vessels (see this 3D model of a blood vessel, spin it around as see the endothelial cells in purple on the inner wall) of both the large and small intestine and the respiratory tract using the angiotensin-converting enzyme 2 (ACE-2) as a binding protein. ACE-2 is embedded in cellular membranes and expressed in several critical tissues, including alveolar lung cells, gastrointestinal tissue and throughout the central nervous system. ACE-2 is important as it acts as a potent negative regulator of the renin angiotensin system (RAS) which controls blood pressure. Dr Craig Daly a vascular scientist from the University of Glasgow talks us through an easy to follow tutorial of the RAS pathway critical for maintaining homeostasis and controlling levels of the hormone angiotensin, which in turn controls blood pressure via constriction and dilation of blood vessels. 

When we are infected with coronavirus, the spike protein on the virus surface binds to ACE-2. Like a key in a lock the cell responds and encapsulates the virus pulling it inside to replicate its ribonucleic acid (RNA), creating a blueprint to potentially make 10-100 of virions that are subsequently released back into the bloodstream ready to infect more cells. 

After SARS-CoV-2 particles leave infected cells, there is a sudden release of inflammatory cytokines which results in leaking of fluid into alveolar sacs in the lungs. This is the ‘cytokine storm’ we hear so much about and this can be devastating if the viral load is too high as we have seen in healthcare workers at the beginning of the pandemic who were poorly equipped with PPE. Systemic inflammatory responses and multiple organ failure tragically cost the life of Dr Li in Wuhan in 2019, the medic who broke the news to the world. As we discovered in the early days, the lungs are unable to remove harmful gases like carbon dioxide and they cannot efficiently provide oxygen to the body. This helps the virus multiply rapidly in the lungs resulting in Acute respiratory distress syndrome. 

While respiratory symptoms are the most common sign of the disease, a recent review suggests 53% of people hospitalized with COVID-19 experience at least one gastrointestinal (GI) symptom during their illness. There is evidence that encountering GI symptoms with COVID-19, or developing them alongside underlying GI conditions like cardiovascular disease or diabetes can also increase the risk of disease severity. More recent research shows that the virus may alter the gut microbiota contributing to nausea and diarrhea. So all those memes of toilet roll are valid! The virus is then free to infect other targets like the central nervous system to cause further damage linked to neurological diseases resulting in long-lasting brain fog.

What natural plant extracts could potentiate some of these pathways?

Much of the latest research on plants used to fight covid symptoms and its after-effects originate from work in Asia and Thailand. It should be remembered that these plants need to be tested together and trials should be properly controlled as some extracts taken in excess or together can have detrimental outcomes. For instance peppermint and black teas can inhibit the absorption of iron, important in the transfer of oxygen to our tissues. So as we propose potential plants that exhibit beneficial effects at the sites of SARS-CoV-2 entry or may provide some inhibitory effects, it should be taken with a degree of optimistic caution in what may provide an alternative to pharmaceutical drugs. 

Physiological effects and mechanisms worth tackling with alternative plant based therapies:

1. Fever control 
2. Calming the cytokine storm 
3. Prevention of viral shedding 
4. Plants that control blood pressure through Angiotensin II or ACE
5. Antagonising the SARs-CoV-2 spike protein
6. Prevention of platelet aggregation
7. Plant based nutrient balance of the renin angiotensin system
8. Boosting the gut microbiome
9. Antifungal activity to combat mucormycosis
10. Diabetes regulation with plant phytonutrients from our previous article 
11. Downstream brain fog with plant phytonutrients from our previous article 

Many plants display antiviral activity and we examine if these theoretically can provide a ‘super tea’ or emollient to reduce symptoms and help people recover from covid infections. Here we describe a few selected plants that are involved in trials (there are too many to provide a complete list but if you are interested reach out and we can discuss further) that could contribute to recovery from Coronavirus highlighting specific traits that potentiate the viral pathway. 

1. Plants that control fever

Indian Frankincense comes from the Boswellia serrata tree, which is native to India, North Africa, and the Middle East. Farmers tap the tree to collect its resin. Boswellia resin and its active ingredient, boswellic acid, appear to have a good anti-inflammatory effect on the body according to a review article suggesting it has good antipyretic (reduces fever) activity.

2. Plants that calm the cytokine storm

Almost all plants will display some anti-inflammatory activity but here we pick out a few that have been studied extensively in peer reviewed journals and have relevance to COVID-19. 

3. Plants that act as detergents preventing Viral shedding 

Butterfly Pea (Clitoria ternatea) is a holy flower in India used in daily puja rituals. The leaves are high in saponins known to act as a detergent which might be useful in removing the spike protein of Coronavirus. It may play an active role in viral shedding as the plant has been identified as a metalloproteinase inhibitor which could disrupt the process reducing the formation of virus. The metalloproteinase, ADAM17 involved in ACE shedding can be targeted using plants like Butterfly Pea as bio based surfactants. It has also been widely used in traditional medicines, and as a supplement to enhance cognitive functions and alleviate symptoms of numerous ailments including fever, inflammation, pain, and diabetes. Although the flower is widely used in teas and colour changing gins, both the seed and roots are not recommended (you can actually be fined in Taiwan for selling it as a foodstuff, butterfly pea is only used for minimal dye levels) as a food source due to much higher levels of saponins. It could however be highly useful as a natural soap based disinfectant in the fight against COVID-19.

4. Plants that control blood pressure through Angiotensin II and ACE

Various medicinal plants have shown inhibitory effects against Angiotensin II, many of which control blood pressure through this mechanism. Our previous EAT THIS blogs describe the actions of many plant based phytonutrients that have actions to reduce blood pressure. 

Pomegranate trees grown in Archangelos, Rhodes – medicine in your own backyard just as the Ancient Greeks would have done. Dr Li, a world renowned physician and scientist, describes how pomegranate promotes good bacteria in the gut, decreasing inflammation and lowering blood glucose levels. 

Pomegranate can be grown from seed in tissue culture to produce healthy clones. Dwarf varieties have potential for greenhouse production similar to blueberries. 

Holy Basil (Ocimum Sanctum) also known as Tulsi has been known to target the reverse transcriptase activity of HIV and theoretically could reduce activity of SARS-CoV-2. The leaves (main photo) contain Eugenol which is an effective treatment for high blood pressure. Just 100g of Basil provides 105% of Vitamin A and 30% of Vitamin C daily requirements. 

Garlic (Allium Sativum)

Anecdotal evidence from our Garlic blog just over a year ago suggests many people found the remedy to alleviate symptoms of covid. Garlic organosulfur compounds, allicin have many medicinal properties that could alleviate Covid 19 symptoms and evidence suggests it can not only  target the viral replication of SARS-CoV-2 but also inhibit ACE activity to dampen Ang II-induced vasoconstrictor responses in blood vessels.

5. Antagonising the spike protein

A study last year found that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 suggesting they could provide a route to prevent cellular infection. 

Neem (Azadirachta Indica) Nimbin extract from Neem is known for its antibacterial properties but molecular docking studies have also proved extracts could have inhibitory activity on the Papain like protease of SARS-CoV-2. Neem extracts have been well documented including inhibitory action against viral activity of herpes, smallpox, chickenpox, HIV.

6. Plants that inhibit platelet aggregation

SARS-CoV-2 and its spike protein directly stimulate platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte–platelet aggregates. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. Critically ill patients diagnosed with COVID-19 may develop a prothrombotic state that places them at a dramatically increased lethal risk so it is important to find ways to inhibit the process. 

Wasabi Japonica is prone to many diseases but clean stock plants can be initiated in tissue culture by ‘The Functional Plant Company’.

Platelet aggregation was first associated with COVID-19 in patients in Wuhan, China as infection produces a prominent elevation of fibrinogen and D-dimer/fibrin degradation products. The damage is caused by the immune system going on the attack (cytokine storm), damaging blood vessel walls and removing several of the normal anti-clotting mechanisms. Essentially the virus causes damage to the lining of blood vessel walls increasing systemic hypercoagulability and blood clots are more likely to form. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients.  

We have previously described the wide range of medicinal properties, anti-microbial, anti-diabetic, anti-asthmatic, anti-cancer, antiviral and anti-fungal in Wasabi Japonica. The active glucosinolate, 6-methylsulfinylhexyl isothiocyanate (6-MSITC) found predominantly in the swollen stem or rhizome of Wasabi as a potential inhibitor of human platelet aggregation in vitro.   

Wasabi ITCs are effective agents for inflammation based on their rapid action and the low levels needed. Isothiocyanates of Wasabi and other crucifers like watercress and broccoli are anti-inflammatory and anti-asthmatic and may provide ease of SARS-CoV-2 symptoms. 

7. Plants can increase essential nutrient levels boosting immunity

Vitamins play a vital role in immune function. 

Patients with severe Covid-19 are reported to be low in both iron and Vitamin D levels and associated with severe acute respiratory disease. These groups include the elderly, people living in the northern hemisphere, obese adults and darker skinned people who produce significantly less Vitamin D and are more likely to be anaemic than other groups.

Low levels of Vitamin D3 actually inhibit renin. Less renin production tips the equilibrium in favour of more Angiotensin II, subsequently raising blood pressure.

Cholecalciferol (Vitamin D3) is a prohormone nutrient synthesised from meat retrieved cholesterol and is processed in the liver using iron as a cofactor for activation.  With increased levels of Vitamin D the expression of proinflammatory cytokines that induce production of C-reactive protein can be significantly diminished. 

There are now calls to supplement daily diets with 1000-2000IU/day Vit D3 to lessen the severity of COVID-19. Vitamin D3 is not a cure for covid-19 but it does have global significance if studies suggest 30-50% of the world’s population are deficient. A study in 2020 showed that a Vitamin D3 blood level of at least 75 nmol/L is needed for protection against COVID-19. An adult needs 4000 IU/day of Vitamin D3 for 3 months to reliably achieve a 75 nmol/L level. People with darker skin need twice as much Vitamin D3 as they produce more melanin which blocks UVB rays and inhibits production of Vitamin D. These doses can greatly reduce the risk of severe illness, but this is not enough for treatment of acute viral infection, which requires a 60,000 to 120,000 IU dose intervention.

Remember that yellow, red and green fruits and vegetables contain beta and alpha carotenoids, lutein, lycopene, zeaxanthin, astaxanthin, β-cryptoxanthin which act as a precursor to Vitamin A. 

Can a plant based diet provide an adequate source of Iron? 

We traditionally consume heme iron from meat, poultry and seafood sources whereas non-heme iron is found in plant foods like whole grains, nuts, seeds, legumes, and leafy greens. Over 79 million people around the world are vegan and don’t eat either meat or dairy products. It was always thought vegans could be deficient in iron due to low absorption of nutrients as our diets change and we move to healthier plant based diets. 

Why is this important? Well heme Iron is absorbed more easily than non heme iron and stored in the body as ferritin, it acts as a cofactor in our blood cells and essential for the uptake of oxygen. We know that SARS-CoV-2 patients have low iron levels which exacerbates oxygen levels to the lungs. 

Some eminent physicians suggest the latter plant based non heme source is adequate for all our iron requirements as we also consume more Vitamin A, C and E from plants which aids non heme iron absorption. Infact, Dr Greger presents data that shows too much heme iron cannot be processed by the body and leads to pro-inflammatory diseases like diabetes and Chronic heart disease.

Life saving high dose Vitamin C

It is becoming clear that high blood levels of not just Vitamin D3 but also Vitamin C are needed to prevent COVID-19 deaths.

Infection triggers a severe inflammatory cellular reaction in the body which results in a decrease in Vitamin C. Along the evolutionary timeline 40 million years ago we lost the ability to make Vitamin C in our bodies due to a genetic mutation.

Unlike most mammals we are unable to synthesize Vitamin C endogenously ourselves so we must access it from our diet. Vitamin C plays an important role in immune function and improves the absorption of nonheme iron, the form of iron present in plant-based foods. It is well understood that insufficient Vitamin C causes scurvy, which is characterized by fatigue. We all know that sailors used a variety of citrus fruits to prevent scurvy but in Scotland where citrus fruits were not abundant they foraged Rock Samphire on the west coast as they found the leaves were high in Vitamin C. Today Rock Samphire is located in only a few inaccessible cliffs but it has potential as a CEA crop.

Kumquat Yuzu (hybrid)

Hesperidin and ascorbic acid in Yuzu counteract the cell damaging effects of the oxygen free radicals triggered by viral infections and inflammation. There is discussion about the preventive efficacy of Vitamin C, at the dose achievable by the diet, as recent reviews suggest it can be useful in the case of strong immune system burden caused by viral disease. 

Today we can access many exotic dried fruits from around the world that are high in Vitamin C including Acerola, Schisandra and Goji berries. Read more about them in our previous EAT THIS articles. Just keep eating those berries! 

8. Plants that boost the gut microbiome 

Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. This change in gut microbiota dysbiosis post disease could contribute to Long haul covid, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19. I have picked out two I grow in controlled environments but there are many fruits and vegetables that act as probiotics (boost gut commensal bacteria) and prebiotic (feed the bacteria).

9. Antifungal activity to combat mucormycosis

Mucormycosis is a serious but rare fungal infection caused by a group of molds called mucormycetes that commonly affects the sinuses or the lungs after inhaling fungal spores from the air. It is caused by exposure to mucor mould which is commonly found in soil, plants, manure, and decaying fruits and vegetables. Increased occurrence of mucormycosis in COVID-19 patients in India is being reported. They require antifungal treatments including liposomal amphotericin B injections but these may lead to side effects. There are many plants with antifungal properties, in fact most of those we describe in this article will have potency against fungal spores. The most accessible include garlic, turmeric and ginger but they should be taken as supplements if fungal disease is suspected. 

Unexpected positive side effects of Covid

Forbes reported on a case in the U.K. of a 61 year old man with aggressive non hodgkin’s Lymphoma going into full remission after contracting COVID-19. While this is an isolated case it gives huge insight into the mechanisms of blood cancer processes and a future opportunity of study. This will undoubtedly lead to understanding new mechanisms linked to cytokine release and the body’s own immune reactions. 

The molecular mechanism by which these medicinal plants target influenza virus can be studied to understand if they attack any molecules overlapping between SARS-CoV-2 and the Influenza viruses. Himalayan forests are abundantly rich in medicinal plant species and a study has documented the presence of ethnomedicinal plants against bronchitis caused by influenza virus, rhinovirus, adenovirus, coronavirus and respiratory syncytial virus.

With emerging Coronavirus variants, there is concern they cannot be quickly and efficiently eliminated in populations across the world leaving us all vulnerable to future pandemics,  or more likely localised epidemics. Regardless, we should be ready and working towards multiple strategies to combat outbreaks and plant biochemistry can play a part if we have peer reviewed studies initiated now. 

Growing plants in Controlled Environment Agriculture

Many if not all these plants can be grown in some form of controlled environment whether it be hydroponics or initiated as clean clones using plant micropropagation. Adapting farms to grow medicinal plants is not difficult and most of these plants will grow in a pH range 6-6.5 with EC 1-1.5 and suitable substrates. The question remains if there is an outlet for this kind of opportunity. That is up to our readers, farmers, growers and academics to address. We have previously discussed many plants that contain phytonutrients and how these can be manipulated using tailored light spectrum and intensity in a clean controlled space which is essential if these plants are to be scaled up for industrial extraction. Consumers should be reassured by these plants being grown in a pesticide and fungicide free environment.  

SUPER TEAS and DETERGENTS – Natural Remedy. 

To summarise, the plants we have selected have the potential to make a ‘super tea’ with active ingredients including isothiocyanate (Wasabi), glycyrrhizin (licorice), quercetin (Hibiscus), eugenol (Holy Basil) suramin (Self heal), hesperidin (Yuzu), ascorbic acid (Samphire), artemisinin-purified and approved (Sweet Wormwood), curcumin (turmeric), withaferin A (Ashwagandha), piperine (black pepper), mangiferin (honeybush), thebaine (poppy), berberine (European barberry, goldenseal, goldthread, greater celandine, Oregon grape, phellodendron and tree turmeric), panduratin A (Galangal), allicin (garlic) and andrographolide (Andrographis). Clear evidence of supplemental Vitamin A, C and D3 supports documented research to reduce Covid-19 disease severity. Emollients made with eucalyptus, Neem, lavender, and frankincense along with nasal sprays incorporating self heal or butterfly pea soaps have potential to provide added protection against coronavirus infections. 

Having read this you may now be wondering, where do I get hold of these wonderful medicinal plants? So at this juncture I urge a little caution, many medicinal plants are available individually as dried root or tea preparations but please ensure you check they are from a reliable and validated source. Combinations can increase efficacy so check this out with your local Chinese herbalist who can advise on TCM. It is best to take professional advice before trying any plant based remedy.

We anticipate CEA farmers or even pharmacologists will want to grow these plants in the future.  If you have an interest in this we would love to engage with you as we have experience of growing a wide range of plants in a controlled environment to produce the highest quality for either study or scaling. Please reach out and consider working with us. 

I am indebted to my friend and colleague UAN & Hort America’s founder and owner Chris Higgins. Without his knowledge, support and encouragement, my entrepreneurial work would not be possible. I am grateful to my friends, physician Dr Barbara Scott MD, Veterinary Lecturer Dr Sally Anne Argyle MRCVS, cardiovascular scientist Dr Craig Daly SFHEA, and Jenny Sim LLP, for their time in reviewing this article. Hort Americas has a full resource and knowledge bank to get you set up growing any of these plants in a controlled environment. 

Disclaimer: We are not advocating this information in preference to medical advice, remember if you have serious illness and symptoms of Coronavirus or Long Covid please seek advice from your general practitioner. Our blogs are designed for people looking for advice on plants that have additional phytonutrients that can help repair the body and boost the immune system. We advise you to stay within peer reviewed research and CDC guidance. 

Unless otherwise stated all images are from plants grown using TC or in CEA by The Functional Plant Company in Scotland and images are the property of Urban Ag News. You can follow The Functional Plant Company on Instagram.The authors declare no affiliation to any companies offering herbal remedies and the information provided is a scientific peer reviewed compilation of plants that provide an opinion of the best potential inhibition of critical pathways involved in SARS-CoV-2 infections. 

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Janet Colston PhD is a pharmacologist with an interest in growing ‘functional’ foods that have additional phytonutrients and display medicinal qualities that are beneficial to human health. She grows these using a range of techniques including plant tissue micropropagation and controlled environmental agriculture to ensure the highest quality control.