In this article we will take a look at biochemical properties of the novel coronavirus, COVID-19, as well as speculate on some potential methods to inhibit it and on ways to help with its known symptoms.
We take a look at compounds, both synthetic and natural, that may inhibit COVID-19 by looking at initial COVID-19 research and what other lipid enveloped viruses are generally vulnerable to. The role of inflammatory response and pneumonia as key symptoms of COVID-19 are also considered.
This article is solely informational and based on scientific and other references. We do not intend to provide any medical advice or recommendations.
We recommend the WHO Mythbusters website as a good resource to verify generic information on COVID-19 that is circulating on the Internet.
A full listing of references can be found at the end of this article.
General properties of the COVID-19
Coronaviruses are so called enveloped viruses: they have a lipid bilayer to protect the protein shell of the virus. Due to their lipid coating, enveloped viruses stick efficiently onto their target cells. They also tend to survive longer than other types of viruses.
Lipid enveloped viruses are capable of adapting their surface appearance to disguise themselves and thereby bypass the host’s immune system without being detected. Examples of lipid coated viruses include Ebola, SARS, MERS, HIV, Herpes, Hepatitis C and the Spanish flu (H1N1).
COVID-19 is airborne and spreads as aerosol. The infection rate is 83% upon exposure, according to The Lancet UK Peer Reviewed Medical Journal.
The incubation period of the COVID-19 is anywhere between 1-27 days after exposure. Chinese officials have confirmed that the virus can be transmitted during the incubation period. A person may test negative, yet be able to spread the virus and then test positive later. It can take up to five testings to find out a person is COVID-19 positive.
Chinese authorities state that the official death rate is around 2%. Other sources put the figure around 1%. Chinese have also released the following, possibly conflicting numbers: 6% survival rate for those who are in serious condition and 1% survival for those in critical condition. According to WHO, 18% of the patients will go into either serious or critical condition.
R0 value shows how many people one infected person will transmit the disease to. Los Alamos National Laboratory in the US estimates the R0 of the COVID-19 to be between 4.7–6.6. R0 of 4 or higher is considered to be uncontainable. In comparison, most viruses have R0 of less than 2.
On the positive side, lipid coated viruses all share similar vulnerabilities. They cannot stand the loss of moisture, or heat or acidic environments. Alcohol or heat sterilize enveloped viruses.
Pneumonia and inflammatory response
The number one cause of suffering due to COVID-19 is pneumonia. Buildup of thick mucus in the respiratory system is also reported.
In pneumonia, inflammatory responses (such as expression of IL-6, IL-10 and TNF secreted proteins and signal molecules) are generally initially elevated to harmful extent. So in the context of COVID-19 it may be prudent to minimize habits and consumables that may unduly spike these immune responses.
Chinese researchers have found that a cause of death for severe and critically ill patients infected with COVID-19 is often the so-called ‘cytokine storm’, an overreaction of the immune system. These patients are found with a higher level of IL-6 in their blood. Last month, the increasing level of IL-6 was recommended as a warning sign that the patient's situation could possibly deteriorate.
Things that are shown to elevate inflammatory responses include generic inflammation, tobacco smoking, excess alcohol, high blood sugar, lack of sleep, lack of exercise, viral and bacterial infections as well as deficiencies in essential micronutrients vitamin D, vitamin C, magnesium, and zinc.
Some immune-supporting supplements that would be otherwise considered beneficial, and might show relative benefits with warding off an infection, are shown to elevate inflammatory responses and avoiding them upon infection should be considered. These include Goji berries, Royal Jelly, Reishi, Grapeseed extract and Astralagus.
Supplements that have been shown to decrease relevant inflammatory responses include, among others, blueberry, vitamin B3 (as Nicotinamide), vitamin C, Spirulina, EGCG, curcumin, resveratrol, inositol, artichoke extract, Boswellia serrata, black seed oil, Rhodiola rosea, PQQ and zinc.
In any case, one needs to consider the unknowns of modulating immune responses (immune suppression or immune stimulation) when having a novel, potent infection.
Can COVID-19 be inhibited?
As of today, the answer to this question is unknown. However, we can take a look at compounds that might inhibit COVID-19 by looking at what other lipid enveloped viruses are generally vulnerable to.
On the synthetic side, Chinese health officials are looking at protease inhibitors to combat COVID-19. Protease inhibitors are a class of antiviral drugs that are used to treat HIV, Hepatitis C, etc. by binding to the viral protease and blocking their replication. Some natural compounds also display protease inhibiting properties.
According to an article published in The Scientist magazine, a COVID-19 patient in Thailand has been successfully treated with a combination of ‘large doses’ of flu drug oseltamivir, combined with HIV drugs lopinavir and ritonavir.
Japanese have reported that an asthma drug appears to be effective in reducing symptoms of coronavirus patients who developed pneumonia.
In order to find novel inhibitors, Chinese scientists have recently screened a compound library of over 687 million compounds against the recently solved structure of the COVID-19. After structural screening, the initial list was narrowed down using different protocols. The relevant study reports a list of 11 drug-like potential compounds, as well as one natural compound of comparable properties.
In the absence of vaccine or working standard treatment, the Chinese have employed a holistic approach and utilized and/or looked at a number of nutritional, drug and combination strategies to combat COVID-19. In addition to compounds addressed in more detail below, these include vitamin A, vitamin E, vitamins B2, B3 and B6, iron, Omega3’s, interferons, gammaglobulin, Thymosin alpha-1, Thymopentin, Levamisole, Cyclosporine A, liquorice root, baicalin, Ginseng saponins, ACE blockers, Chloroquine, Emodin, Promazine, Ribavirin, Lopinavir, Remdesivir, Nitric Oxide, Alpha Lipoic Acid and select phytoestrogens and flavonoids.
Select natural compounds in relation to coronaviruses and flu-type symptoms
Here we take a look at some more common supplements that have been suggested across the Internet to provide help with COVID-19, its symptoms or suppression, in one way or another.
This list is by no means comprehensive. Other compounds that would deserve a closer look include Active Hexose Correlated Compound, Echinacea, select medicinal mushrooms, beta-glucans, garlic, lactoferrin, and more.
While many supplements and natural treatments are being promoted or utilized to prevent or treat the novel coronavirus, none have been proven to work, but some do display possible benefits and potential for wider utilization and development.
Some supplements have evidence for relative prevention or symptom reduction, but that’s for flu, common cold or other types of coronaviruses – nobody knows how well this evidence applies to COVID-19. As of today, the extent of these benefits is unknown – and in any case they are relative and case-specific.
Although there is no direct evidence at this time to suggest that using zinc lozenges can prevent or treat COVID-19 in people, zinc displays anti-viral properties and was shown in a laboratory study to inhibit the replication of coronaviruses in cells.
Zinc deficiency may make you more susceptible to pneumonia and zinc supplementation may reduce the chance of death from pneumonia.
Zinc lozenges or other orally dissolving zinc formulas such as sprays containing correct forms of zinc have been shown to reduce the severity and duration of colds caused by viruses. They appear to do this by acting directly in the throat, which is why the timing and duration of use matters when treating colds in the oral cavity with zinc.
Beyond this local effect, it should be noted that supplementing with zinc would not benefit most people unless they are deficient in zinc. Deficiency is more common in elderly people due to reduced zinc absorption. In such people, supplementing with zinc may improve the chance of avoiding respiratory tract infection.
Others who may be low in zinc include people taking stomach acid reducers and ACE inhibitors as medication on a long-term basis.
Vitamin C is vital to the function of leukocytes, blood cells that combat infections, and overall immune system health. Vitamin C is also important for iron absorption, and being deficient in iron can make you more vulnerable to infections in general.
Even for common colds, the evidence that vitamin C supplements can help is modest: taking high-dose vitamin C before getting a cold may slightly reduce the severity and duration of a cold, but there is inconclusive evidence as to whether taking vitamin C will help after or during the cold symptoms develop.
There is no evidence that taking a vitamin C supplement, even at high doses, can protect people from infection from coronaviruses.
However, high doses of intravenous vitamin C are currently being tested in COVID-19 patients in China who have developed pneumonia, but the benefit of this approach has yet to be proven.
Vitamin D supplements, taken daily in moderate doses, may help to reduce the risk of respiratory infections and viruses such as influenza A in children and adults who are deficient or severely deficient in vitamin D.
Although there is not currently any research suggesting vitamin D supplements decrease the risk of coronavirus infection specifically, maintaining an adequate blood level of vitamin D (20 to 30 ng/mL) by getting proper sun exposure at least three times a week for about 30 minutes, or consuming vitamin D-fortified products, or taking a vitamin D supplement is a good and safe preventative measure for protecting against respiratory infections in general.
Monolaurin - Lauric acid - Coconut Oil
Monolaurin is a metabolite of lauric acid, a compound found in coconut oil. Monolaurin displays powerful antiviral activity against multiple lipid enveloped viruses.
There is no evidence to date that consuming coconut oil can prevent or treat coronavirus infections in people.
Researchers have proposed a clinical trial using virgin coconut oil, monolaurin, and/or monocaprin (800 mg daily) in patients with COVID-19. This proposal has been published on the Integrated Chemists of the Philippines website.
Laboratory evidence suggests honey has anti-influenza properties, but there have been no human trials to verify this.
Relatively stronger evidence indicates that honey may help with cough, which is supported by traditional use of honey for this purpose.
Elderberry extract has been shown in laboratory studies to inhibit the replication of human flu viruses, including certain strains of Influenza A and B, and H1N1.
Small, preliminary trials in people with the flu suggest that, taken within the first day or so of experiencing symptoms, elderberry may shorten the duration of the flu, but more studies are needed to verify this.
There is no evidence that elderberry extract can prevent COVID-19 or reduce symptoms in people who have been infected.
NAC is an acetylated form of the amino acid cysteine. In the body, NAC helps the synthesis of the endogenous antioxidant glutathione, which plays a critical role in the immune system. NAC may improve symptoms of influenza-induced pneumonia.
There is evidence that NAC may improve certain blood markers of immune system health, but there is limited evidence to suggest that NAC supplementation improves the immune system to the extent that it would reduce the occurrence of illness – or prevent coronavirus infection.
NAC supplementation aids lung function in general and may be of help in instances of mucus buildup.
EGCG, epigallocatechin gallate, a bioactive compound of green tea has been shown to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV.
EGCG has been shown to damage or alter most lipid enveloped virus particles, including HIV, HCV, influenza, and HSV. EGCG is able to bind to HIV-1 and prevent it from infecting the targeted cell.
EGCG might prove to be an inhibitor of COVID-19, of unknown potency and subject to further research.
With regards to pneumonia, EGCG may help suppress excess inflammatory responses.
Selenium deficiency has high implications in viral infections. The selenium deficient regions are more susceptible to HIV infections in the population and HIV infection rates are the highest where selenium intake is the lowest.
Research has shown that a strain of influenza virus exhibits increased virulence when given to Selenium deficient mice.
Selenium deficiency also leads to low glutathione levels and thereby impairs the working of the immune system.
Spirulina, green blue algae, is available on the market as a superfood and a nutrient-dense supplement.
Spirulina displays multiple antioxidant, anti-cancer, immunomodulating, and antiviral properties. According to the Journal of Microbiology and Biotechnology, green blue algae contains powerful protease inhibitors.
In laboratory tests, Spirulina is capable of inhibiting several lipid enveloped viruses such as herpes and HIV.
Spirulina also inhibits select inflammatory responses (IL-6), so it may also be helpful in reducing the autoimmunity challenges caused by ongoing COVID-19 infection.
Quercetin - Isoquercetin
A number of flavonoids are being investigated in relation to COVID-19 due to their antiviral properties. One of the promising ones is quercetin, or its derivative isoquercetin. Isoquercetin is a polymorphic compound that can be isolated from plants such as rheum nobile, mango, noble rhubarb and sikkim rhubarb.
Quercetin has been shown to be a long lasting anti-inflammatory substance that possesses strong anti-inflammatory capacities.
Isoquercetin has been shown to inhibit the replication of both influenza A and B viruses at the lowest effective concentration. In a mouse model of influenza virus infection, isoquercetin administered to mice inoculated with human influenza A virus significantly decreased the virus pathological changes in the lung.
Research suggests that isoquercetin may have the potential to be developed as a therapeutic agent for the treatment of influenza and COVID-19 virus infections and for the suppression of resistance in combination therapy with existing drugs.
For further reading, we recommend Examine.com’s Corona resource:
WHO Mythbusters website https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters
Article ‘Coronavirus contagious even in incubation stage, China’s health authority says’, South China Morning Post, Jan 26th, 2020. https://www.scmp.com/news/china/society/article/3047701/coronavirus-contagious-even-incubation-stage-chinas-health
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, Volume 395, February 15, 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated. Los Alamos National Laboratory. https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1.full.pdf
China repurposes AbbVie HIV drug as Big Pharma rallies to combat deadly coronavirus. FiercePharma, Jan 27., 2020. https://www.fiercepharma.com/pharma-asia/china-repurposes-abbvie-hiv-dug-as-big-pharma-rallies-to-help-combat-deadly-coronavirus
Article ‘Flu and HIV Drugs Show Efficacy Against Coronavirus’, The Scientist, Feb. 3, 2020.
Asthma drug seems effective for COVID-19 pneumonia. NHK World, March 3, 2020. https://www3.nhk.or.jp/nhkworld/en/news/20200303_20/
Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 687 Million Compounds. ChemRxiv 03.03.2020. https://chemrxiv.org/articles/Inhibitors_for_Novel_Coronavirus_Protease_Identified_by_Virtual_Screening_of_687_Million_Compounds/11923239
I-Mab Biopharma Announces Development of TJM2 to Treat Cytokine Release Syndrome Associated with Severe and Critically-Ill Patients with Coronavirus Disease (COVID-19). Biospace, March 13, 2020. https://www.biospace.com/article/releases/i-mab-biopharma-announces-development-of-tjm2-to-treat-cytokine-release-syndrome-associated-with-severe-and-critically-ill-patients-with-coronavirus-disease-covid-19-/
Potential treatments to defeat novel coronavirus. Xinhua, March 07, 2020. http://en.people.cn/n3/2020/0307/c90000-9665722.html
Blueberries reduce pro-inflammatory cytokine TNF-α and IL-6 production in mouse macrophages by inhibiting NF-κB activation and the MAPK pathway. Mol Nutr Food Res. 2011 Oct;55(10):1587-91. https://www.ncbi.nlm.nih.gov/pubmed/21887820
Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013 Dec;24(12):2076-84. https://www.ncbi.nlm.nih.gov/pubmed/24231099
Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells. Journal of Virology Sep 2004, 78 (20) 11334-11339. https://jvi.asm.org/content/78/20/11334
Potential interventions for novel coronavirus in China: A systematic review. Journal of Medical Virology, 13 Feb, 2020. https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25707
Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis. Arch Intern Med. 2007 Aug 13-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495652/
The Role of Interleukin 6 During Viral Infections. Front. Microbiol., 10 May 2019. https://www.frontiersin.org/articles/10.3389/fmicb.2019.01057/full
IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harb Perspect Biol. 2014 Oct; 6(10): a016295. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176007/
Natural compounds as inflammation inhibitors. Genes Nutr. 2011 May; 6(2): 89–92. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092910/
Natural anti-inflammatory agents for pain relief. Surg Neurol Int. 2010; 1: 80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011108/
Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 2013 Aug; 169(8): 1672–1692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753829/
In Silico Discovery of Plant-Origin Natural Product Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL). Front. Pharmacol., 25 July 2018. https://www.frontiersin.org/articles/10.3389/fphar.2018.00800/full
Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010 Nov 4;6(11):e1001176.
Zinc: a new risk factor for pneumonia in the elderly? Nutr Rev. 2010 Jan; 68(1): 30–37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854541/
Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial. The Lancet,September 17, 2005. https://www.thelancet.com/journals/lancet/article/PIIS0140673605671097/fulltext
Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia. ClinicalTrials.gov Identifier: NCT04264533. https://clinicaltrials.gov/ct2/show/NCT04264533
Vitamin D and Influenza—Prevention or Therapy? Int J Mol Sci. 2018 Aug; 19(8): 2419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121423/
RANDOMISED DOUBLE BLIND STUDY TO COMPARE EFFECTIVENESS OF HONEY, SALBUTAMOL AND PLACEBO IN TREATMENT OF COUGH IN CHILDREN WITH COMMON COLD. East Afr Med J. 2014 Feb;91(2):50-6. https://www.ncbi.nlm.nih.gov/pubmed/26859020
IN VITRO EFFECTS OF MONOLAURIN COMPOUNDS ON ENVELOPED RNA AND DNA VIRUSES. Journal of Food Safety, March 1982. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1745-4565.1982.tb00429.x
A Review of Monolaurin and Lauric Acid: Natural Virucidal and Bactericidal Agents. Alternative and Complementary Therapies Vol. 12, No. 6, Dec. 11, 2006. https://www.liebertpub.com/doi/abs/10.1089/act.2006.12.310?journalCode=act&
Extreme Sensitivity of Enveloped Viruses, Including Herpes Simplex, to Long-Chain Unsaturated Monoglycerides and Alcohols. Antimicrob Agents Chemother. 1979 Jan; 15(1): 67–73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC352602/
Potential of Complementary and Alternative Medicine in Preventive Management of Novel H1N1 Flu (Swine Flu) Pandemic: Thwarting Potential Disasters in the Bud. Evid Based Complement Alternat Med. 2011; 2011: 586506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957173/
Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019 Feb;42:361-365. https://www.ncbi.nlm.nih.gov/pubmed/30670267
Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review. Phytother Res. 2018 May;32(5):811-822. https://www.ncbi.nlm.nih.gov/pubmed/29356205
N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia. Medicine (Baltimore). 2018 Nov; 97(45): e13087. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250560/
The role of adjuvant immunomodulatory agents for treatment of severe influenza. Antiviral Res. 2018 Feb; 150: 202–216. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801167/
High-dose N-acetylcysteine therapy for novel H1N1 influenza pneumonia. Ann Intern Med. 2010 May 18;152(10):687-8. https://www.ncbi.nlm.nih.gov/pubmed/20479037/
Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009; 30(1-2): 1–12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696075/
Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol. 2013 Mar; 168(5): 1059–1073. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594666/
Preclinical Development of the Green Tea Catechin, Epigallocatechin Gallate, as an HIV-1 Therapy. J Allergy Clin Immunol. 2009 Feb; 123(2): 459–465. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665796/
Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway. Gene. 2014 May 25;542(1):46-51. https://www.ncbi.nlm.nih.gov/pubmed/24630969
Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections. Adv Nutr. 2015 Jan; 6(1): 73–82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288282/
Selenium Deficiency and Viral Infection. The Journal of Nutrition, Volume 133, Issue 5, May 2003. https://academic.oup.com/jn/article/133/5/1463S/4558528
The Role of Selenium in HIV Infection Cosby A Stone, Kosuke Kawai, Roland Kupka, Wafaie W Fawzi Harvard School of Public Health. Nutr Rev. 2010 Nov; 68(11): 671–681. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066516/
Activation of the human innate immune system by Spirulina: augmentation of interferon production and NK cytotoxicity by oral administration of hot water extract of Spirulina platensis. Int Immunopharmacol. 2002 Mar;2(4):423-34. https://www.ncbi.nlm.nih.gov/pubmed/11962722
Antioxidant, Immunomodulating, and Microbial-Modulating Activities of the Sustainable and Ecofriendly Spirulina. Oxid Med Cell Longev. 2017; 2017: 3247528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274660/
Isolation and structure determination of a proteasome inhibitory metabolite from a culture of Scytonema hofmanni. J Microbiol Biotechnol. 2008 Oct;18(10):1655-8. https://www.ncbi.nlm.nih.gov/pubmed/18955814
Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnology Letters 34(5):831-8, February 2012. https://www.researchgate.net/publication/221847568_Flavonoid-mediated_inhibition_of_SARS_coronavirus_3C-like_protease_expressed_in_Pichia_pastoris
The Lazaridis Family Foundation contributes $1 million to the IRCM to support its research on the COVID-19 coronavirus. Montreal Clinical Research Institute, March 4, 2020. https://ircm.qc.ca/en/news/lazaridis-family-foundation-contributes-1-million-ircm-support-its-research-covid-19
Inhibition of influenza virus replication by plant isoquercetin. Antiviral research 88(2):227-35 · November 2010. https://www.researchgate.net/publication/46180681_Inhibition_of_influenza_virus_replication_by_plant_isoquercetin
Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine. Sci Rep. 2016; 6: 19095. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709578/
Quercetin, Inflammation and Immunity. Nutrients. 2016 Mar; 8(3): 167. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808895/