Herbal Antivirals, Supplements, and Covid-19 - a Look at the Research

7/27/2022

Disclaimer: Information for research purposes only. Should you need medical treatment, seek the care of a qualified medical or complementary medicine practitioner. Herbal medicines have cautions, contraindications, and herb/drug interactions. Your individual risk factors should be assessed. Safety, quality, and efficacy are all important aspects of herbal medicine, and vary widely across the industry. Chinese medicine should always be used with the supervision of a licensed Chinese medicine practitioner.

In no way does the information in this article attempt to diminish the helpfulness of Western antivirals when available and indicated. The U.S. has an FDA approved Paxlovid therapeutic treatment to prevent very serious illness when taken early. Ask your MD if you qualify for access. https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19. Some patients who experienced improvement of Covid-19 symptoms while under treatment of Paxlovid experienced a rebound effect. Scientists began working on the assumption that the dose and length of treatment may not have been sufficient for the viral load in these cases, despite high efficacy in preventing death. https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf.

Sadly, not every country, nor every person in the U.S. has access to high quality Western treatment. Problems lacking health insurance or resources to access the U.S. healthcare system still abound in the United States.

It is the opinion of this author that vaccines are helpful to both individuals and society as a whole, and none of the information regarding herbal medicine and supplements should be construed to be utilized in lieu of vaccination. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-myths/art-20485720.

Given the highly contagious BA.5 strain currently dominant, along with the debilitating severity of long-covid, efforts to prevent and mitigate risk are strongly indicated, especially since people can become reinfected with strains of Omicron as soon as four weeks after a previous infection.

Single Herbs: Lysine, Qing Hao (Artemesia), over-the counter (OTC) immune-system agents (Zinc, Quinine, Quercetin, Vit E, Vit D3, Vit C), and Black Seed or Black Seed Oil have peer-reviewed evidence listed below (research highlighted is not exhaustive of the available research on these herbs).

Other single herbs you may be interested in researching include: Lian Qiao (Forsythia), Jin Yin Hua (Flos Lonicerae Japonicae), Huang Qin (Radix Scutellariae), Da Qing Ye (Folium Isatidis), Cat’s Claw, Goldenseal (endangered).

The single herbs above are not exhaustive of the herbs that can have an effect on SARS-CoV-2. In addition to the common herbs above, the following herbs can also act as agents that inhibit various pathways of SARS-CoV-2, reduce inflammatory cytokines, and reduce damage to lungs and tissues.

Curcumin (Curcuma Longa L., Curcuma phaeocaulis Val.) (Jiang Huang, E Zhu), Citrus sinensis (Chen Pi), Diosmetin (Citrus aurantium L.) (Zhi Shi), Cimicifuga foetida L. (Sheng Ma), Melia azedarach L. (Ku Lian Pi), Coptis chinensis Franch (Huang Lian), Phellodendron chinense Schneid. (Huang Bai), and Sophora flavescens Ait. (Ku Shen), Rheum officinale Bail1. (Da Huang), Polygonum multiflorum Thunb. (He Shou Wu), and Caulis Polygoni multiflori (Shou Wu Teng), Sambucus williamsii Hance (Jie Gu Mu), Urtica fissa E. Pritz. (Xun Ma), Andrographis paniculata (Burm. f.) Nees (Chuan Xin Lian), Ephedra sinica Stapf. (Ma Huang)–Prunus armeniaca L. (Ku Xing Ren), Glycyrrhiza uralensis Fisch. (Gan Cao), Caffeic acid phenethyl ester (Cinnamomum cassia Presl.) (Rou Gui), Honokiol (Magnolia officinalis Rehd. et Wils.) (Hou Po), Cordyceps sinensis extract (Cordyceps sinensis (Berk.) Sacc.), Cordyceps sinensis extract (Cordyceps sinensis (Berk.) Sacc.), Ruscogenin (Ophiopogon japonicus (L.f) Ker-Gawl) (Mai Dong), Tanshinone IIA (Salvia miltiorrhiza Bge.) (Dan Shen), Isoforskolin (Sparganium stoloniferum Buch.-Ham.) (San Leng), Saikosaponins (Bupleurum chinense DC.) (Chai Hu).

Chinese Medicine Formulas: The following Chinese medicine formulas have been studied extensively in multiple trials. Huoxiang Zhengqi Wan (Agastache Qi-Correcting Pills), Lianhua Qingwen Zhiji (Forsythiae and Honeysuckle Flower Pestilence-Clearing Preparations), ShufengJiedu Keli (Wind-Expelling and Toxin-Removing Granules), and Fangfeng Tongsheng
Zhiji (Saposhnikoviae Heat-Clearing Preparations) Qingfei Paidu Tang (Lung-Cleansing and Toxins-Removing Decoction) (list not exhaustive, but indicative of the accepted protocol in China, after 7 trial iterations early in the pandemic).

LYSINE:

Lysine is an essential amino acid that has a long history of helping to suppress the herpes simplex virus (HSV) (herpes simplex 1 generally causes cold sores, herpes simplex 2 generally causes genital herpes, although some crossover can occur). The action of Lysine can be both inhibitory if taken preventatively, or can facilitate recovery during an outbreak.

In contrast, the amino acid, Arginine, can feed the HSV, leading to outbreaks. L-Arginine is common in several different food categories. Occasionally, someone might be surprised at the outbreak of cold sores and then realize they recently began consuming large amounts of almond milk. Therefore, examining dietary triggers and aids can be helpful in suppressing viral load.

To inhibit viral load, a person should consider increasing the ratio of Lysine to Arginine, but keep in mind that some of the same foods rich in Lysine are also rich in Arginine. Therefore, herbal supplement of Lysine may provide some benefit.

Good sources of Lysine include foods that are rich in protein, such as:

Meat, specifically red meat, pork, and poultry.
Cheese, particularly parmesan.
Certain fish, such as cod and sardines.
Eggs. (some arginine in eggs https://healthyeating.sfgate.com/larginine-eggs-1602.html)
Soybeans, particularly tofu, isolated soy protein, and defatted soybean flour.
Spirulina. https://www.healthline.com/health/healthy-high-arginine-foods#spirulina
Fenugreek seed (ratio of lysine is greater than arginine) https://www.thepharmajournal.com/archives/2021/vol10issue8/PartY/10-8-208-327.pdf

https://www.mountsinai.org/health-library/supplement/lysine

Foods that are high in protein naturally contain L-Arginine including:

Meat (red meat, chicken, turkey).
Fish (salmon, haddock).
Nuts and seeds (almonds, cashews, pumpkin seeds).
Legumes (soybeans, chickpeas).
Whole grains (brown rice, oats).
Dairy products (milk, yogurt, cheese).

https://my.clevelandclinic.org/health/drugs/22536-l-arginine

As you can see above, many of the same foods high in Lysine are also high in Arginine. Seeking a higher Lysine to Arginine ratio is desired to suppress viral activity (example: Fenugreek seed). For this reason, supplemental Lysine is sometimes helpful. If you do take a supplement, I recommend high quality vegetarian capsules, without fillers or stearate as binders. (available on https://wellevate.me/Innovations-to-Wellness for 10% off MSRP)

LYSINE and SARS-CoV-2

How does Lysine interact with Covid-19? In the peer-reviewed, evidence-based journal of Viruses, one study found that Lysine can inhibit the virus at early stages of SARS-CoV-2 and may act as a helpful supplement in prevention.

These authors confirmed the finding re: Arginine and Herpes in relation to other viruses like Covid-19 and Influenza A (Arginine increases the activity of Covid-19 and Influenza A (IAV)).

Therefore, while Lysine appears to inhibit viral activity, Arginine appears to increase viral loads.

Melano I, Kuo LL, Lo YC, Sung PW, Tien N, and Su WC, Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection. Viruses. 2021 Jul: 13(7): 1301.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310019/#:~:text=Lysine%20and%20Lys%2Dester%20can,COVID%2D19%20and%20flu%20patients.

These authors found that Lysine could reduce viral load, showing that:

“Lysine and Lys-ester can attenuate SARS-CoV-2 infection in the cell culture system (Figure 2A). Consistent with a previous study, IAV replication was also inhibited by lysine (Figure 4) [20]. Lysine therapy has long been recommended against HSV infection because it can suppress viral replication and inhibit virus yield [23,26,27,28,38].”

“Possible mechanisms for the suppressing of SARS-CoV-2 could occur at the fusion peptide and endosomal membrane, potentially disrupting the release of virus particles. Another possible mechanism could result from lysine’s ability to reduce intracellular calcium levels. The authors conclude that, L-“Lysine and Lys-ester can prevent SARS-CoV-2 and IAV infection, particularly in the entry stage. In contrast to that, Arg-ester can potently boost infection of both viruses. It would therefore be beneficial to consider the nutrient intake of COVID-19 and flu patients.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310019/#:~:text=Lysine%20and%20Lys%2Dester%20can,COVID%2D19%20and%20flu%20patients.

These author’s findings reinforce the protective effect of looking at your dietary intake in addition to possible recommendations of Lysine supplementation in both prevention and early treatment of Covid-19. Decreasing Arginine intake is also important.

While Lysine demonstrates good effect among early, mild, and moderate Covid, L-Lysine should be used with caution among patients with severe Covid, at least those with high fever. https://www.science.org/do/10.1126/comment.742380/full/

Zinc: (available on https://wellevate.me/Innovations-to-Wellness 10% off MSRP)

Zinc: “Zn+2 mediates numerous non-specific and specific immunological functions:(16,17) From normal development and function of cells,(18,19) including those regulating nonspecific immunity, inter alia, activity of natural killer (NK) cells and neutrophils, and macrophage function; to maintaining expression of tight-junction proteins between lung-lining muco-epithelial cells, blocking entry of pathogens; from increasing cilia length and ciliary beat-frequency in those cells’ mechanical clearance of surface “litter” such as virus particles, and repair of such function in coronavirus-damaged lung cells; to immune response modulation,(20,21) tamping down on overshooting inflammatory immune responses(22) (thus preventing, for example, high levels of inflammatory mediators such as destructive reactive oxygen and nitrogen species) and normalizing the ratios of diverse immune cell types. Additionally, zinc is strongly implicated in inhibiting viral binding to cell membrane ACE2 receptors used by the coronavirus to latch onto the outside of potential host cells as an essential step preparatory to entering and invading those cells; and for its inhibiting effect on functioning of viral replication enzymes such as retroviral RNA replicase,(23) thus blunting the attack by those virus particles that do gain entrance to host cells.”

Melano I, Kuo LL, Lo YC, Sung PW, Tien N, and Su WC, Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection. Viruses. 2021 Jul: 13(7): 1301.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310019/#:~:text=Lysine%20and%20Lys%2Dester%20can,COVID%2D19%20and%20flu%20patients.

Caution in taking Zinc at high levels, as toxicity can occur from excessive doses. Take only at approved levels.

Quinine water is readily available in the United States. For safe sourcing of Quinine, see original article.

Quinine: “has also been shown to have an independent anti-viral activity against the COVID-19-causing SARS-CoV-2 coronavirus.(29) Additionally, there is evidence of an anti-TNFa effect of quinine(30) that may be contributory to the assumed protective anti-inflammatory effect for COVID-19 patients. For example, research on IBD patients relative to SARS-CoV-2 shows possible protective effects of anti-TNFa antibodies in Crohn’s patients.(31).”

Quercetin: (available for 10% off MSRP) on
https://wellevate.me/Innovations-to-Wellness)

Quercetin: “a bioflavonoid polyphenol, has been shown to act as a zinc ionophore,(32) enhancing entrance of zinc into cells to inhibit viral intracellular replication. It is also believed to block viruses from entering cells in the first place. An Oak Ridge National Labs/University of Tennessee study of many FDA-approved compounds presented supercomputer modeling results for inhibition by them of SARS-CoV-2 viral S-spike binding to cells. The study ranked quercetin as fifth out of 20 top performers.(33) Studies have shown quercetin also exhibiting anti-inflammatory properties,(34-36) which could help mitigate the inflammatory response of cytokine and/or bradykinin storms provoked by COVID-19. A wide range of anti-viral/immunity benefits of quercetin have been identified,(37-41) as well as other health benefits that may address some comorbidities of COVID-19(42-44) and some of its sequelae(44,45).”

Lyposomal Vitamin C: (available for 10% off MSRP) on
https://wellevate.me/Innovations-to-Wellness)

Vitamin C: “Effects of vitamin C on the immune system (e.g., possible enhancement of activity of NK cells and of other effectors of immunity mechanisms) are well documented. Administration of vitamin C before or after the appearance of flu symptoms seems to, respectively, prevent or ameliorate/alleviate flu symptoms in test populations relative to control populations.(46) Metadata analysis of dozens of studies covering thousands of common cold episodes demonstrated regular supplementation with vitamin C correlating with a modest but consistent reduction in duration of cold symptoms.(47)”

Vitamin K2/D3: (K2 helps with D3 absorption - available for 10% off MSRP on
https://wellevate.me/Innovations-to-Wellness)

Vitamin D3 with K2: “COVID-19-related recommendations for vitamin D3 supplementation may go beyond compensation for low UVB (approx. 320-280 nm) exposure directed to restore patients’ D3 levels reduced by pandemic-mitigating lockdown/ shut-in restrictions. Review studies support a protective role of vitamin D3 supplementation in prevention of acute respiratory tract infection.(48) Recent reports suggest that vitamin D3 plays a significant role in immune system function(49) and, in particular, in susceptibility to COVID-19(50).” Vitamin K2 helps in the absorption of Vit D3.

Vitamin E: (available available for 10% off MSRP on
https://wellevate.me/Innovations-to-Wellness)

Vitamin E: “has been shown to enhance immune system function and reduce risk of infection, particularly in older individuals, via modulation of T cell function by directly impacting T cell membrane integrity, signal transduction and cell division, and by indirectly affecting inflammatory mediators generated by other immune cells.(51) There are additional data suggesting vitamin E’s role in modulation of macrophages, NK cells and B cells.(52)”

L-Lysine: (available for 10% off MSRP on
https://wellevate.me/Innovations-to-Wellness)

L-Lysine: “has been shown to improve immune system function.(53) The mechanism of immunological enhancement by which l-lysine supplementation reduces infection rates is thought to be via its raising of zinc serum levels, apparently by facilitating zinc absorption from the gut; additionally, CD4 T cell count shows an increase.(54).

The authors of “Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection” found a strong statistical significance in favor of the effectiveness of the above OTC formulations “for prevention and treatment of (retro)viral infections, inclusive of COVID-19, over a 20-week period”, even when adopting low assumptions/estimates for the widespread Covid-19 virus spread patterns during the time of the study.

For citations within text, more information re: methods, study design, and analysis, please see original article in Journal of Evidence-Based Integrative Medicine. https://journals.sagepub.com/doi/pdf/10.1177/2515690X211026193

Qing Hao (Artemesia, a commonly used treatment for malaria) and SARS-CoV-2

Qing Hao (Artemesia) has received widespread acknowledgement in the treatment of malaria since at least 2001, when it was recognized by the WHO. But how does it interact with Covid-19? Artemisia was utilized in 2003 during the SARS-CoV-1 outbreak, and scientists recently studied its impact on SARS-CoV-2.

Law S, “Is the Traditional Chinese Herb Artemisia annua possible to fight against Covid-19?”, Integr Med Res. 2020: Sept; 9(3): 100474. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362865/

“The pharmacological mechanism of Artemisia annua has mainly inhibited the enzymatic activity of CLPro (chymotrypsin-like protease) which is an enzyme produced by SARS-CoV-2 during COVID-19 infection. It is expected to be improved exhausting adaptive immunity and modulating the inflammatory response through regulating the production of pro-inflammatory cytokines such as prostaglandin E2 (PGE2), IL-6, IL-10 and TNF alpha. The genesis of CD4, CD8 and interferon-gamma would be increased when a combination of the minerals and biomolecules. The principle is the same as artemisinin-based combination therapies (ACTs) and well developed previously in 2003.(5)

Limitations of Qing Hao:

“Artemisinin is the most important bioactive component in Artemisia annua. . . . However, artemisinin has certain limitations such as poor water insolubility and bioavailability, so various semi-synthetic derivatives developed including dihydroartemisinin, β-artemether and artesunate which exhibit greater potency, improve the water solubility, favorable metabolic as well as the hydrolytic https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362865/

Qing Hao must be carefully sourced for quality and safety and is not as ubiquitously available as Lysine. In Chinese medicine, Qing Hao is not usually utilized in isolation, but in balanced formulas that treat holistically.

Additional resources studying the impact of Qing Hao (Artemisia annua) can be found here:

Fuzimoto A. “An Overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment.” J Integr Med. 2021 Sep.

and here:

“The combination of A. annua's biological properties, action on different signaling pathways and target proteins, and a multi-drug combined-therapy approach may synergistically inhibit SARS-CoV-2 and assist in the COVID-19 treatment. Also, A. annua may modulate the host immune response to better fight the infection.”

https://pubmed.ncbi.nlm.nih.gov/34479848/#:~:text=annua's%20biological%20properties%2C%20action%20on,to%20better%20fight%20the%20infection

Black Seed or Black Seed Oil (Nigella Sativa), also called Black Cumin Seeds

Khazdair MR, Ghafari S, Sadeghi M. “Possible therapeutic effects of Nigella Sativa and its thymoquinone on Covid-19.” Pharm Biol. 2021; 59(1): 696–703.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204995/

These authors investigated the mechanisms involved with Black Seed or Black Seed Oil (Nigella Sativa) finding evidence to support that “N. sativa and TQ reduced the level of pro-inflammatory mediators including, IL-2, IL-4, IL-6, and IL-12, while enhancing IFN-γ. Nigella sativa and TQ increased the serum levels of IgG1 and IgG2a, and improved pulmonary function tests in restrictive respiratory disorders.” They concluded that “N. sativa and TQ might have beneficial effects on the treatment or control of COVID-19 due to antiviral, anti-inflammatory and immunomodulatory properties as well as bronchodilatory effects”, encouraging additional clinical studies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204995/

Three additional resources investigating the role of Black Cumin Seeds in potential therapeutic effect on Covid-19 include:

Mohamed N, Maideen P. “Prophetic Medicine-Nigella Sativa (Black Cumin Seeds) - Potential Herb for Covid-19? J Pharmacopuncture. 2020 Jun 30; 23(2): 62–70. This study examines the “antiviral, antioxidant, anti-inflammatory, anticoagulant, immunomodulatory, bronchodilatory, antihistaminic, antitussive, antipyretic and analgesic activities” of N. Sativa. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338708/.
Haidairi A, A.A. K., Faiq T, Ghareeb O. Clinical Trial of Black Seeds Against Covid-19 in Kirkuk City/Iraq. Indian Journal of Forensic Medicine and Toxicology; 15(3):3393-3399, 2021. In this study, among 419 patients divided into two groups, “a significantly higher severity of infection among control group 44 (17.0%) than the black seed group were noticed; the control group also showed 14 deaths (5.4%), while there were no deaths in black seeds group (0.0%).” https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/en/covidwho-1302972.
Badary OA, Hamza MS, Tikamdas R. Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure. Drug Design, Development and Therapy. 3 May 2021 Volume 2021:15 Pages 1819—1833. In this study, the authors outline the various volatile oils that are included in Black Seed. https://www.dovepress.com/thymoquinone-a-promising-natural-compound-with-potential-benefits-for--peer-reviewed-fulltext-article-DDDT.

“Nigella sativa (Black seed), from the family Ranunculaceae, have been found in several ancient sites, including Tutankhamun’s tomb. The Persian physician Avicenna, regarded as the father of early modern medicine, described the plant in his Canon of Medicine as offering a treatment for shortness of breath,32 which frequently accompanies pathological conditions such as asthma and pneumonia. Volatile oils and alkaloids are generally associated with biological activity, and the volatile oils of these seeds contain nigellone, thymoquinone (TQ), thymohydroquinone, dithymoquinone, thymol, carvacrol, α and β-pinene, d-limonene, d-citronellol, p-cymene, carvacrol, t-anethole, 4-terpineol and longifolene.(33,34) Nigella sativa seeds thus offer a natural product with multiple potential pharmacological activities including antidiabetic, anticancer, immunomodulatory, analgesic, antimicrobial, anti-inflammatory, bronchodilator, renal and gastro-protective, and antioxidant properties.(35,36)“ https://www.dovepress.com/thymoquinone-a-promising-natural-compound-with-potential-benefits-for--peer-reviewed-fulltext-article-DDDT.
Subsequently diving deeper into the main volatile oil found in Black Seed. "Thymoquinone (2-Isopropyl-5-methylbenzo-1, 4-quinone) is the main active ingredient of the volatile oil of black seed (Figure 1). It was first extracted by El–Dakhakhny,(37) and amongst the various different active constituents reported so far, TQ remains the major bioactive principle due to its range of therapeutic benefits including antioxidant,(38) anti-inflammatory,(39) anti-cancer,(40) antibacterial,(41) antifungal activity,(42) and anticonvulsant activity.(43) Furthermore, a more specific effect of the antiviral activity of TQ and black seed fixed oil against murine cytomegalovirus infection model has been reported.(44,45) “ https://www.dovepress.com/thymoquinone-a-promising-natural-compound-with-potential-benefits-for--peer-reviewed-fulltext-article-DDDT.
Specifically, these authors examine the effects of Black Seed on antioxidant, anti-inflammatory, immunomodulatory, epigenetic modulatory, anti-viral, molecular docking, anti-bacterial, anti-coagulation effects on Covid-19 along with effects on comorbidities. The authors conclude that Black Seed can be useful in conjunction with other therapeutics in the treatment of Covid-19. https://www.dovepress.com/thymoquinone-a-promising-natural-compound-with-potential-benefits-for--peer-reviewed-fulltext-article-DDDT

These articles just scratch the surface on studies done on Black Seed. A quick peer-reviewed search includes many others, including, but not limited to:

Thymoquinone’s Antiviral Effects: It is Time to Be Proven in the Covid-19 Pandemic Era and Its Omicron Variant Surge.
https://www.frontiersin.org/articles/10.3389/fphar.2022.848676/full
and:
Antiviral effects of black seeds: Effect on COVID-19. https://www.sciencedirect.com › science › article › pii

Chinese Medicine Formulas and Covid-19:

All of the examples above have been presented in Western fashion, as separate herbs, with an examination of the function and mechanism of each independently. However, in the application of Chinese medicine, herbal supplements are rarely used in isolation, but rather in balanced formulas, used in conjunction with other herbs. Chinese medicine formulas are paired with the extensive diagnostic pattern differentiation process, applied based on signs/symptoms, asking questions, looking (tongue diagnosis, color, etc), listening, and palpation (e.g. feeling pulse - see this post for an introductory glimpse into the art of Chinese pulse palpation) http://www.innovationstowellness.com/blog/chinese-pulse-diagnosis-the-art-of-palpation.

The treatment of Covid-19 with Chinese medicine both overlaps pharmacologically with Western medicine, but also extends into the long-tested clinical traditions of Chinese medicine.

“Most fundamental theories of traditional Chinese medicine [TCM] are founded on the Huang Di Nei Jing (Yellow Emperor's Inner Classic), an ancient Chinese medical text written in the 2nd century BCE. This text mentioned the idea of “prevention before disease occurrence”, and the strategies of “prevention of transmission after occurrence” and “prevention of recurrence after recovery”. The measures to “prevent before disease occurrence” include staying away from the source of infection, cutting off the route of transmission, minimizing the environmental impact on susceptible population, and building the body's self-defending ability against pathogens. After disease occurrence, active measures need to be taken to prevent mild conditions from developing into severe or critical ones. It is also important to take precautions to prevent recurrence upon recovery.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

These ancient guidelines are similar to the modern day strategies of epidemiology and public health prevention to minimize the impact of epidemics and pandemics. However, the method of treatment in Chinese medicine retains unique adherence to a holistic view, rather than solely a mechanistic method.

“Unlike evidence-based modern medicine, traditional Chinese medicine is an empirical medicine developed on accumulated clinical observations gathered over centuries of practice. It not only deals with the etiological factor to eradicate the pathogenic microbial, but also supports the body's immune function to help fight the disease and ameliorate its consequences. In ancient times, when facing infectious disease, specific pathogens could not be identified; however, doctors could observe the patient's signs and symptoms, assess the condition and develop strategies and formulas for the different stages of the illness.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/pdf/main.pdf

The authors of this article, Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/, go into great detail on the application of several Chinese medicine formulas implemented to treat Covid-19 early in the pandemic, before vaccines were available. I highly recommend reading it in its entirely if you are interested in the mechanisms and pathopharmacology of the formula interventions.

Three patent medicines were initially studied: (Lianhua Qingwen Keli/Jiaonang (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), Jinhua Qinggan Keli.

In trial version 4, the study examined: (Huoxiang Zhengqi Wan (Agastache Qi-Correcting Pills), Lianhua Qingwen Zhiji (Forsythiae and Honeysuckle Flower Pestilence-Clearing Preparations), Shufeng Jiedu Keli (Wind-Expelling and Toxin-Removing Granules), and Fangfeng Tongsheng
Zhiji (Saposhnikoviae Heat-Clearing Preparations)

In trial version 6 and 7, the specific protocol recommendation included: “Qingfei Paidu Tang (Lung-Cleansing and Toxins-Removing Decoction), along with modified formulas for different stages (mild, moderate, severe, critical, and convalescence). In addition, Fangfeng Tongsheng Zhiji was removed from the recommended lists of Chinese patent medicine (Table 2).”

At the time of publication of the above article, April 2020, an evidence-base had already begun to be established:

“over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The results of 16 published papers on this topic (not including case reports) and a systematic review on 8 clinical trials (804 cases) have suggested that integrated traditional Chinese and Western medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever(16).”
“According to a retrospective study on 1305 COVID-19 cases treated in Wuhan University Tongren Hospital, patients who took Chinese medicine preparations had a smaller death risk than those who did not (0.273, P < 0.05);”

Searches of MEDLINE, EMBASE, WANFANG DATA and CNKI included:

“16 clinical trial papers on traditional Chinese medicine/integrated traditional Chinese and Western medicine for COVID-19(27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,) involving a total of 1529 cases (shown in Table 4). Preliminary study findings have shown that integrated traditional Chinese and Western medicine had a shorter time to defervescence than standard Western medicine treatment alone.”
“A multicenter, prospective, and randomized controlled trial (n = 284) showed Lianhuaqingwen Capsule, a repurposed marketed Chinese herb product, could be considered to ameliorate clinical symptoms of COVID-19. Compared with control group, the recovery rate (91.5% vs. 82.4%, P = 0.022), the rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, P < 0.001) and clinical cure (78.9% vs. 66.2%, P = 0.017) were significantly higher, the median time to symptom recovery (median: 7 vs. 10 days, P < 0.001), time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) were significantly shorter in treatment group(42).”
“Another retrospective analysis on 308 cases(34) have suggested that, after receiving traditional Chinese medicine treatment, all mild and moderate COVID-19 cases recovered and none became severe/critical.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

Initial application of Chinese medicine formulas began with the history of treatment of SARS in late 2002, 2003.(44). Research demonstrated that while different from the specifically targeted activities of Western medications.

“TCM exerted broad-spectrum antiviral and immune regulatory effects to treat COVID-19.”
“Lianhua Qingwen Capsules exerted its anti-coronavirus activity by inhibiting the SARS-CoV-2 replication and reducing the cytokine release from host cells, thus supporting the clinical application for COVID-19(45).”
”Liu Shen Capsule significantly inhibited SARS-CoV-2 replication in Vero E6 cells, greatly reduced the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10), and regulated the activity of NF-κB/MAPK signaling pathway in vitro(46).”
“With multiple components, multiple targets and multiple links, compound Chinese medicine formulas produce an overall regulation of the body. Studies have shown that some Chinese medicine indirectly inhibit virus growth via host-directed regulation to boost the immune function of the host or inhibit virus-mediated inflammatory response, and some Chinese medicine can directly exhibit broad-spectrum antiviral effects, such as Jin Yin Hua (Flos Lonicerae Japonicae), Huang Qin (Radix Scutellariae) and Da Qing Ye (Folium Isatidis)(47).”
“ In the past decade, scientists have confirmed multiple components in TCM with immune regulatory and antiviral activity. Due to the similarity of SARS-CoV-2 and other RNA viruses, these naturally occurring compounds from TCM in previous studies may have the capacity to inhibit SARS-CoV-2(44). Yang et al.(44) have summarized TCM herb formulae against SARS-CoV and ongoing TCM clinical trials for the treatment of SARS-CoV-2 infection.”
“Moreover, through analysis of historical records on prevention and treatment of SARS and H1N1 influenza infections and the frequency of TCM used in 23 provinces, Luo et al.(48) concluded that the most frequently used herbs contained Astragali Radix (Huang Qi), Radix glycyrrhizae (Gan Cao), Saposhnikoviae Radix (Fang Feng), Atractylodis Macrocephalae Rhizoma (Bai Zhu), Lonicerae Japonicae Flos (Jin Yin Hua), and Forsythia Fructus (Lian Qiao).” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

In addition to the broad antiviral effects, TCM treatment addresses the massive inflammatory pathway in conjunction with immune system regulation and promoting healing.

“Host-directed regulation COVID-19 caused by SARS-CoV-2 is mainly associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine responses(45,49). TCM works not only to inhibit the virus, but to block the infection, regulate the immune response, cut off the inflammatory storm, and promote the repair of the body(50), such as Lianhua Qingwen Capsules, which suppressed the increased cytokine (TNF-α, IL-6, CCL-2/MCP-1, and CXCL-10/IP-10) release in a dose-dependent manner, when host cells were infected with HCoV-229E and SARS-CoV-2(45).”
“Since viral pneumonia involves infection, inflammation, immune response, blood coagulation, tissue injury, and genetic polymorphism, Ye et al.(51) constructed a component-target-pathway to analyze the components in Lianhua Qingwen Capsules and pathways to boost immunity, such as T cells, B-cell receptor signaling, natural killer (NK) cell-mediated cytotoxicity, and anti-inflammatory Fc epsilon RI, ErbB, and MAPK signaling pathways. Of ten inflammatory and immune signals, formononetin, rutin, emodin 8-O-β-d-glucoside, hyperoside, loganic acid, and salidroside are more important than the other components.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939

Therefore, the Lianhua Qingwen Capsules studied appeared to have antiviral effects, anti-inflammatory mechanisms, and immune-system modulation in their therapeutic activity. Other formulas also have multiple pathways towards healing.

“Network pharmacological study(52) has suggested that the compound formula Qingfei Paidu Decoction contains 948 chemical components, which act via modulation of 790 potential target proteins. The protein–protein interactions may form a molecular network. As modulations of these targets may regulate immunity- and cytokine-related pathways, inhibit the activation of cytokines, and thus mediate overactive immune response and reduce inflammation, multiple active components of Chinese medicine have been found to protect organ damage from virus infection, virus replication and secondary inflammatory factors. Liu et al.(53) studied major chemical components in Qingfei Paidu Decoction and tissue distribution in mice using UHPLC–Q-Orbitrap HRMS technology. They identified 39 chemical components, among which 9 can be rapidly absorbed and distributed over multiple tissues. Except for baicalin (exhibited a peak value at 2 or 4 h), the serum and tissue concentrations of the other eight components in exhibited a peak value within 0.5 h. At 0.5 h, the exposed components in the lung tissues (in sequence) are ephedrine, prunasin, pseudoephedrine, amygdalin, hesperidin, irisflorentin, baicalin, hyperin, and liquiritin; and the concentrations of ephedrine, prunasin, pseudoephedrine and baicalin remained high at 2 and 4 h. These findings provided pharmacokinetic information for its further efficacy study and clinical use. Previous studies have suggested that ephedrine, pseudoephedrine and amygdalin have notable anti-inflammatory(54) and immunomodulatory actions(55), and therefore, are main components in therapeutic drugs for respiratory disorders. Zhang et al.(56) found that amygdalin could protect acute lipopolysaccharide (LPS)-induced lung damage through inhibiting nuclear factor kappa-B (NF-κB) and LRR and PYD domains-containing protein 3 (NLRP3) signaling pathways.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

Additional evidence regarding potential targets in the treatment of Covid-19 were found:

“Network pharmacology and molecular docking have also been used in potential targets and action mechanism of recommended formulas in the Diagnosis and Treatment Protocol for COVID-19(57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71). In traditional Chinese medicine treatment protocol for COVID-19, Xuanfei Paidu Keli (Lung-Dispersing and Toxins-Removing Granules), Shengjiang San, Sangju Yin (Mulberry Leaf and Chrysanthemum Beverage), Yinqiao San (Lonicera and Forsythia Powder), Lianhua Qingwen Jiaonang (Forsythiae and Honeysuckle Flower Pestilence-Clearing Capsules), Maxing Shigan Tang (Ephedra, Apricot Kernel, Gypsum and Licorice Decoction), Maxing Yigan Tang (Ephedra, Apricot Kernel, Coicis and Licorice Decoction), Haoqin Qingdan Tang (Sweet Wormwood and Scutellaria Gallbladder-Clearing Decoction), Xueshi Wuye Lugen Tang (Xue's Five Leaves Reed Rhizome decoction) and Kangbingdu Keli (anti-viral granules) work for both the virus and human body; Huoxiang Zhengqi Formula, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Maxing Shigan Tang, Xuebijing Injection, Qingfei Paidu Tang, Dayuan Yin (Arecae and Magnoliae Officinalis Liquid), Xiaochaihu Tang (Minor Bupleurum Decoction), Shashen Maidong Tang (Glehniae and Ophiopogon Decoction), Qingwen Baidu San (Epidemic-Clearing Toxin-Resolving Powder), Shenzhu San (Atractylodis and Angelicae Dahuricae Powder), Huanglian Jiedu Tang (Coptis Toxin-Resolving Decoction), Shengmai Injection and Xuebijing Injection can help with COVID-19 cases by reducing expression of inflammatory factors, inhibiting cytokine storm, decreasing oxidative stress and apoptosis, boosting immune functions, regulating energy metabolism, promoting nutrient absorption and metabolism, improving cardiopulmonary function, and modulating nervous system.”
“Some Chinese medicine directly exhibit broad-spectrum antiviral effects, some were found to possess their anti-coronaviruses effects via potential targets such as SARS-CoV-2 3CL protease, RNA dependent RNA polymerase (RdRp), papain-like protease (PLpro), helicase, and spike glycoprotein (Spike).”
“Ye et al.(51) studied the molecular mechanism of Lianhua Qingwen Capsules for COVID-19 via molecular docking. By docking and scoring of 21 compounds and SARS-CoV-2 3CL protease, they found that the scores of rutin, forsythoside B and hyperoside are higher than lopinavir; and hyperoside might be the most potential SARS-CoV-2 3CL protease inhibitor.”
“Wu et al.(57) systematically analyzed all the proteins encoded by SARS-CoV-2 genes, selected a total of 21 targets, including two human targets (ACE2 and TMPRSS2) and screened a ZINC drug database (2924 compounds) and natural products database of their own (containing 1066 chemicals), and a database of 78 anti-viral drugs using target-based computer virtue screening. They found that some natural flavanoids, licoflavonol from Glycyrrhiza uralensis, cosmosiin from Scutellaria baicalensis, neohesperidin from Citrus aurantium, mangostin from Garcinia mangostana, kouitchenside D from Swertia kouitchensis, excoecariatoxin from Excoecaria agallocha, phyllaemblicin G7 from Phyllanthus emblica, and piceatannol from Vitis vinifera, exhibited high binding affinity. The only compound that could target the binding interface between Spike and ACE2 was hesperidin. This study provided new lead compounds, targets and research strategy for further in vivo and in vitro anti-SARS-CoV-2 research.”
“Chinese medicinal plant Jin Yin Hua (Flos Lonicerae Japonicae) can remarkably inhibit influenza virus(72), EV71(73), and Dengue virus type 2(74). Its active antiviral components include chlorogenic acid(75), flavonoids and triterpene saponins(76). It is a major component of Yinhuang Injection, Shuanghuanglian Injection, Yinhuang Tablets, Vitamin C Honeysuckle Pills and Yinhuang Tablets, which are commonly used for fever and respiratory tract infections(77).”
“Huang Qin (Radix Scutellariae) can inhibit respiratory syncytial virus, influenza virus and Coxsackie virus(78, 79, 80). Its chemical components include flavonoids, flavonols (baicalin, baicalein, wogonoside, wogonin, dihydrobaicalin, etc.), terpenoids, volatile oil, trace elements and polysaccharide(81). Rao and his team(82) screened baicalein, a SARS-CoV 3CL protease inhibitor, and assumed that flavonoids have the similar activity as they share the similar structure. Enzyme inhibitory assays have found that scutellarein, quercetagetin, myricetin and robinetin can inhibit SARS-CoV 3CL protease. During the study on active anti-SARS-CoV compounds, we screened a natural product quercetin-3-β-galactoside, a potential SARS-CoV 3CL protease inhibitor, from MDL-ACD database. Its inhibition mechanism has been confirmed by molecular simulation, point mutation experiment, FRET method and SPR technology(83). The components of Shuanghuanglian Oral Liquid are Jin Yin Hua (Flos Lonicerae Japonicae), Huang Qin (Radix Scutellariae) and Lian Qiao (Fructus Forsythiae). Recent studies reported the first family case of COVID-19 achieved rapid recovery to combined Western medicine and Shuanghuanglian Oral Liquid without obvious adverse reactions; however, sufficient evidence is needed for recommended clinical use84. Recently, shikonin as an active ingredient derived from Lithospermum erythrorhizon Sieb. et Zucc was reported to have the inhibitory activity against SARS-CoV-2 3CL protease with IC50 of 15.75±8.22 μmol/L(85).”
“The main components of Lianhua Qingwen Capsules include Lian Qiao (Fructus Forsythiae), Jin Yin Hua (Flos Lonicerae Japonicae) and Zhi Ma Huang (Herba Ephedra Praeparata cum Melle). It has been proven to have broad-spectrum activities (IC50 = 0.35–2 mg/mL) against influenza virus, including H7N9. It can effectively damage the nuclear export signals of nucleocapsid protein (RNP) and at the same time, regulate viral infection-induced immune response, and reduce levels of inflammatory cytokines during early infection(86). What's more, it can significantly inhibit the SARS-CoV-2 replication, affect virus morphology and exert anti-inflammatory activity in vitro. These findings indicate that it protects against the virus attack and thus, can be used as a novel strategy for controlling the COVID-19(87)”
“Lianqiao Baidu Pian (Forsythia Toxin-Resolving Tablets), Xiongju Shangqing Wan (Chuanxiong and Chrysanthemum Pills) and Qingwen Baidu Pian (Epidemic-Clearing Toxin-Resolving Tablets) have better anti-coronavirus effects. Compound Qinlan (Scutellariae and Isatidis) Oral Liquid and Reyanning Mixture have shown a good anti-HCoV-229E efficacy, probably by inhibiting viral replication within the lung, improving gastrointestinal function, boosting the immune function and reducing the expression of inflammatory cytokines within pulmonary cells(88,89). These Chinese medicines and their components provided reference for anti-SARS-CoV-2 drug screening and clinical treatment as well as the R&D of anti-coronavirus drugs.” Ni et al. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

Excerpts have been presented above, for the complete study, please see all of the data here: Ni L, Chen L, Huang X, Han C, Xu J, Zhang H, Luan X, Zhao Y, Xu J, Yuan W, Chen H. “Combating Covid-19 with Integrated Traditional Chinese and Western Medicine in China.” Acta Pharm Sin B. 2020 Jul: 10(7):1149-1162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319939/

Despite the substantial and far-reaching implications of the treatment of Covid-19 with Chinese medicine, as evidenced by the various pathways, mechanisms, and broad inflammatory reduction and immune-boosting actions of the formulas outlined in the article above, some limitations for their use exist specifically within the United States, because of the inclusion of Ma Huang in many of the above verified treatments for Covid-19.

Ma Huang (a particularly important herb used in the treatment of lung conditions, channel obstruction, colds and flus) was misused by Western pharmaceutical companies in dangerous ways and subsequently banned for use in the United States. Ma Huang is contraindicated for sweating, cardiovascular disorders, and high blood pressure; common contraindications learned during the 3-4 years of intensive training received by Chinese medicine students in the United States. Ma Huang should not be combined with other stimulants, should be cooked appropriately (at least 45 minutes, draining and discarding the froth off from the top), and should be monitored carefully with only short-term use. Instead of being utilized safely, within the safety and preparation methods utilized in Chinese medicinal use, the components in Ma Huang were taken out of its safely monitored Chinese medicinal use context and were used inappropriately, as highly concentrated ephedra and promoted in opposition to its contraindications as a weight loss drug -which it is not a Chinese medicinal indication for Ma Huang-it is indicated to support the lungs or certain types of pain in Chinese medicine). https://www.pacificcollege.edu/news/blog/2014/07/07/ma-huang-herb-misused-and-abused

As a result of the FDA ban on Ma Huang, practitioners in the United States are not allowed to use it safely for its intended use to support the lungs. As a result, many of the formulas for treating Covid-19 listed above must be modified, and equivalent research and data without the use of Ma Huang is not available. Modifications are frequently used by Chinese medicine practitioners, as formulas are often tailored for an individuals’ signs/symptoms, pattern; however, the efficacy of Ma Huang replacements are not identical.

Pharmacokinetic Properties of Chinese Medicine on SARS-CoV-2

Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

The authors above found inhibitory effects on SARS-CoV-2 and sequelae by single herbs that included: Curcumin (Curcuma Longa L., Curcuma phaeocaulis Val.) (Jiang Huang, E Zhu), Citrus sinensis (Chen Pi), Diosmetin (Citrus aurantium L.) (Zhi Shi), Cimicifuga foetida L. (Sheng Ma), Melia azedarach L. (Ku Lian Pi), Coptis chinensis Franch (Huang Lian), Phellodendron chinense Schneid. (Huang Bai), and Sophora flavescens Ait. (Ku Shen), Rheum officinale Bail1. (Da Huang), Polygonum multiflorum Thunb. (He Shou Wu), and Caulis Polygoni multiflori (Shou Wu Teng), Sambucus williamsii Hance (Jie Gu Mu), Urtica fissa E. Pritz. (Xun Ma), Andrographis paniculata (Burm. f.) Nees (Chuan Xin Lian), Ephedra sinica Stapf. (Ma Huang)–Prunus armeniaca L. (Ku Xing Ren), Glycyrrhiza uralensis Fisch. (Gan Cao), Caffeic acid phenethyl ester (Cinnamomum cassia Presl.) (Rou Gui), Honokiol (Magnolia officinalis Rehd. et Wils.) (Hou Po), Cordyceps sinensis extract (Cordyceps sinensis (Berk.) Sacc.), Cordyceps sinensis extract (Cordyceps sinensis (Berk.) Sacc.), Ruscogenin (Ophiopogon japonicus (L.f) Ker-Gawl) (Mai Dong), Tanshinone IIA (Salvia miltiorrhiza Bge.) (Dan Shen), Isoforskolin (Sparganium stoloniferum Buch.-Ham.) (San Leng), Saikosaponins (Bupleurum chinense DC.) (Chai Hu).

The formulas Li et al. tested and found to have inhibitory effects on SARS-CoV-2 included: Qingfei Paidu decoction (QFPD), the Huashi Baidu formula (HSBD), Ma Xing Shi Gan decoction (MXSGD) the Xuanfei Baidu decoction (XFBD), the Jinhua Qinggan granule, the Lianhua Qingwen capsule/granule (LHQW), and the Xuebijing injection (XBJ).

For a complete list of compounds, specific pathways of interaction, and pharmacokinetic data investigated, please see the authors’ original article here: Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

Li et al. first outline the mechanisms of Covid-19:

“In the human body, angiotension-converting enzyme 2 (ACE2) is responsible for the regulation of blood pressure. ACE2 is widely expressed in the nasal mucosa, bronchus, lungs, heart, esophagus, kidneys, stomach, bladder, and ileum, all of these organs are vulnerable to SARS-CoV-2(15). In addition, ACE2 has been identified as the receptor of SARS=CoV-2 on the human cell membrane. ACE2 mediates the entry of SARS-CoV-2 into host cells by interacting with the S protein. Hence ACE2 plays a key role in viral infection (16).”

“Figure 1: Pathogenesis of COVID-19. After entering the human body, SARS-CoV-2 invades cells by binding with ACE2 and begins to replicate in the cytoplasm of the host cells. The virus is presented to B and T cells by macrophages and dendritic cells, while the host immune system is simultaneously activated. B and T cells are differentiated into effector immune cells, inducing the production of proinflammatory cytokines and chemokines. However, continuous activation of the immune system and accumulation of cytokines can lead to uncontrolled cytokine storm, causing the lungs and other organs to be seriously injured by SARS-CoV-2 infection. MODS: multiple organ dysfunction syndrome; TMPRSS2: transmembrane protease serine 2; Th: T helper cell; CTL: cytotoxic T lymphocyte; DC: dendritic cell; NK: natural killer; Tn: naive T cell; Mφ: macrophage.”
Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

For a complete list of compounds, specific pathways of interaction, and pharmacokinetic data investigated, please see the authors’ original article.

“Figure 2: Antiviral action by TCM. TCM inhibits infection of SARS-CoV-2 through multiple mechanisms, including prevention of the activity of ACE2 and the S protein by directly binding with them, downregulating the expression of the receptors of the S protein (e.g., ACE2 and angiotensin II receptor type 2 (AGTR2)), and inhibiting viral replication by suppressing the expression of RdRP and 3CLpro. The representative TCMs related to each mechanisms are listed in the green boxes. Mpro: main protease; sgRNA: single guide RNA.”
Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

For a complete list of compounds, specific pathways of interaction, and pharmacokinetic data investigated, please see the authors’ original article.

These authors also documented the anti-inflammatory mechanisms of TCM on the immune system.

“Figure 3: TCM immune modulation and anti-inflammation. TCM treats SARS-CoV-2 infection by modulating the host immune system, which includes increasing the production of interferons (IFNs) at the onset of the disease, inhibiting Toll-like receptor (TLR)-mediated inflammatory response, suppressing the production of proinflammatory cytokines, and inducing the differentiation of T and B cells into effector immune cells. The representative TCMs acting on each pathway are listed in the green boxes. CD: cluster of differentiation; ISG: interferon-stimulated gene; AT: alveolar type.”
Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

For a complete list of compounds, specific pathways of interaction, and pharmacokinetic data investigated, please see the authors’ original article.

The authors continued to investigate the influence on lung deterioration related to Covid-19 and found protective effects within the lungs as well.

“Figure 4: Suppression of lung injury and fibrosis by TCM. TCM reduces lung injury and pulmonary fibrosis by inhibiting inflammation-related and oxidation-related pathways, such as by downregulating the expression of cytokines, inflammasomes, and reactive oxygen species (ROS); suppressing alveolar neutrophil infiltration; inhibiting NF-κB, nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), and TLR-mediated pathways; and reducing oxidative stress. The representative TCMs acting through each pathway are listed in the green boxes. NLRP: nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor; MMP: matrix metalloproteinase.”
Li L, Wu Y, Wang J, Yan H, Lu J, Wan Y, Zhang B, Zhang J, Yang J, Wang X, Zhang M, Li Y, Miao L, and Zhang H. “Potential Treatment of COV ID-19 with Traditional Chinese Medicine: What Herbs Can Help Win the Battle with SARs-CoV-2?” Engineering. 2021: Oct 28. Doi: 10.1016/j.eng.2021.08.020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552808/

For a complete list of compounds, specific pathways of interaction, and pharmacokinetic data investigated, please see the authors’ original article.

As you can see from the very brief overview of highlighted single herbs and herbal formulas above, the peer-reviewed evidence base for the use of herbal treatments as therapeutics and in treatment of the negative sequelae for the damage caused by Covid-19 is quite extensive. As more research articles are funded and executed, more evidence on the helpfulness of complementary medicine in conjunction with Western therapeutics is likely. Given the extensive and continuing widespread community exposure worldwide and the devastating effects people have reported suffering from long-Covid, it is useful to examine and research all methods available for helping the health of individuals and entire population groups improve.

1 Comment

James Roninger

7/27/2022 04:23:27 pm

Hi Dr. Crystal. My name is James, I lived in the Gold Coast neighborhood from 2004-2010. I believe we were acquaintances. Well, since then I enrolled in the masters in Nutrition program at Bastyr University. Since Covid happened, I took an interest in herbal antivirals. Your email is very comprehensive! I have been brainstorming a diagram showing the basic mechanisms of action for the best antiviral constituents. Perhaps you know of someone who would like to collaborate?

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Herbal Antivirals, Supplements, and Covid-19 - a Look at the Research

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