Potential Therapeutics for Protection Against COVID-19

Written by Devin Wilson, ND, CCT – April 9, 2020

“prevention is better than cure”.

Presented below are protection strategies that include specific anti-viral approaches, as well as approaches to help one’s immune system stay in a anti-inflammatory state and ready to fight infection.

The strategies include rationale for various natural agents such as vitamin D, vitamin A, zinc, colloidal sliver, and others, as well as drugs such as hydroxychloroquine and Zithromax. The role for stem cells and exosomes to regulate the immune response to a viral infection is also included.

SCIENCE: Biology of the coronavirus, SARS-CoV-2 – A quick review

ACE2, not just a doorway for viruses to enter cells

Similar to its relative, SARS-CoV, which caused the 2003 SARS outbreak, the SARS-CoV-2 virus, enters human cells using an enzyme called angiotensin-converting enzyme 2 (ACE2) as a doorway. ACE2 is found in many tissues but especially high levels in the lung.

Considering the virus uses ACE2 to enter cells there is concern that increasing it may lead to increased risk of infection and severity of COVID-19. However, this is speculation and there is no clinical evidence supporting it. On the contrary, restoring ACE2 levels may be protective.

ACE2 has powerful anti-inflammatory and immune modulating effects but when levels are reduced these beneficial effects are lost. As COVID-19 progresses it causes a state of “ACE2 exhaustion” where ACE2 levels are significantly diminished due to viral particles binding them. Low levels of ACE2 are believed to be responsible for the severe cases of COVID-19 with acute respiratory distress syndrome (ARDS), pneumonia and lung damage. Studies have shown the importance of ACE2 in regards to lung health and underlying conditions that increase the risk of severe COVID-19.

Low ACE2 is closely associated with acute respiratory disease syndrome (ARDS) and restoring ACE2 may protect against acute severe lung injury commonly seen in COVID-19.

Low ACE2 may also exacerbate underlying cardiovascular conditions including high blood pressure, atherosclerosis, heart failure, kidney disease, serious lung injury, and others. Disease models have demonstrated that the loss of ACE2 function can lead to increased neutrophils (a type of white blood cell) in the lung, exaggerated inflammation and lung injury.

Despite the speculative concern that restoring ACE2 may exacerbate COVID-19, there is ample evidence drawn from previous studies to support its beneficial role. Many natural agents can improve ACE2 and are presented below.

3CL Protease

Once inside human cells the process of cellular take over begins and the virus starts to replicate. The virus also begins damaging cells by producing an enzyme called 3CL Protease. This enzyme not only damages cells and causes inflammation; it allows the virus to spread to other nearby cells. Inhibiting this viral enzyme may be beneficial in reducing tissue damage and spread of the virus. Many natural agents can inhibit 3CL Protease and are presented below.

Evading the innate immune system

Even after the virus enters cells and begins replication it still needs to evade our innate immune system, a specialized subset of immune cells and proteins that kill viruses.

Viruses have many mechanisms to evade the immune system thus supporting the innate immune response will likely be helpful to prevent infection and reduce risk of progressing to severe COVID-19. Furthermore, those with a weakened immune system are at risk and may greatly benefit from such preventative immune support.

COVID-19 prevention with natural substances, drugs and advanced therapies

There are a number of things you can do to prime your body in case of infection. These are not necessarily treatments but are preventative strategies that may help you reduce risk of infection and support you being part of the 80% with minimal to mild symptoms and a quick recovery. These strategies have the greatest chance of success if they are started before you are exposed.

Improving ACE2

In addition to regular exercise and a plant-based whole foods diet many natural agents have shown to improve ACE2. This includes curcumin, resveratrol, rosmarinic acid, and alpha lipoic acid. In addition to its effect on ACE2, resveratrol has been shown to inhibit the growth of the MERS corona virus and reduce corona virus induced inflammation.

Inhibiting 3CL Protease

Many natural substances can be used to inhibit the 3CL protease enzyme that the virus produces to damage cells and spread infection. Elderberry fruit inhibits this enzyme and has also been shown to reduce corona virus activity in cells. It seems to be most effective when taken prior to infection and during the initial infection period. Ground flax seed has also been suggested due to its content of herbacetin, a potent inhibitor of 3CL protease.

Supporting the Innate Immune System

The innate immune system is present at birth and is your biggest ally against most infections. Its function is supported by many things including ample sleep, exercise and a healthy diet. Protein is the most important dietary component as protein deficiency impairs innate immunity.

Beyond sleep, exercise and diet, many natural substances can be used to support the immune system. Some of the most important substances include vitamin D, vitamin A, vitamin C and Zinc.

Melatonin and mushroom extracts can also have beneficial effects as they both support the immune system to fight viruses. Melatonin also reduces inflammation caused by corona virus infection.

Probiotics may also be beneficial in COVID-19 as they support the innate immune system by balancing the gut microbiome. Probiotics with the best evidence for immune stimulation are Lactobacillus species commonly found in fermented foods and Bacillus species.

In addition to natural supplements more advanced therapies such as stem cell therapy and exosome therapy may be beneficial for prevention COVID-19. Two trials have already demonstrated promising results and a number of other trials are currently underway.

Protective Effects: Vitamin D

As it pertains to the current pandemic, Vitamin D has been shown to reduce the risk of respiratory infection (1, 2, 3), modulate the immune system, enhance immune cell function, reduce mortality in older adults, and reduce inflammation and cytokines that cause “cytokine storms”. A cytokine storm is a severe overreaction of the immune system in response to an infection such as SARS-CoV-2 that can be life threatening. In fact, many severe cases of COVID-19 and related deaths are thought to be due to cytokine storms as they can cause severe inflammation, tissue damage and organ failure.

Taking Vitamin D may be especially important for the aging population and those who have low levels. Vitamin D deficiency is very common in older adults, who are most at risk for severe symptoms and death due to COVID-19. Low Vitamin D has been associated with the increased risk of pneumonia in adults, increased risk of viral pneumonia in children, and increased risk of mortality in patients with pneumonia. It has also been suggested that people lacking vitamin D have a weaker innate immune defense against SARS-CoV-2.

In addition, mounting evidence suggests that Vitamin D deficiency may be linked with cardiovascular conditions such as high blood pressure, diabetes and heart disease, all of which have been shown to increase the risk of severe cases of COVID-19.

Anti-Viral Effects: Colloidal Silver

Prior to the advent of antibiotics, silver was known for its therapeutic properties and commonly used to treat infections. While there is no clinical evidence showing that silver is effective against viruses in humans the antimicrobial properties of silver have been confirmed.


Experimental studies have shown silver to be effective against several types of bacteria, and viruses including corona virus. A 2009 study revealed that silver reduced viral activity of a coronavirus strain commonly used as a model for the 2003 SARS virus by 90% within 60 minutes of exposure and by 99.99% after 24 hours of exposure. Silver has also been shown to be active against other viruses including human imunodeficiency virus (HIV), hepatitis B virus, herpes simplex virus (HSV), and respiratory syncytial virus (RSV).


Despite the lack of human evidence regarding the anti-viral effects of ingesting silver we use colloidal silver extensively in our practice without any safety issues. Proper formulations of very low parts-per-million (PPM) nanoparticles, silver colloid such as Sovereign Silver, will not accumulate in body tissue and is extremely safe. Gargling and use of nasal spray preparations MAY reduce viral loads, if used several times a day.


Anti-Viral Effects: Vitamin C


Vitamin C a common supplement used to support the immune system may also be useful in COVID-19. Vitamin C has been shown to improve anti-oxidant status, decrease inflammation, exert strong anti-viral effects. Vitamin C may also help prevent acute respiratory distress syndrome (ARDS) and acute lung injury. Early clinical trials from China have already demonstrated positive effects of both oral and intravenous vitamin C in COVID-19 patients. In fact, the government of Shanghai, China recently announced its official recommendation that COVID-19 should be treated with intravenous vitamin C. Additionally, the Chinese government has recommended 2-3 grams of oral vitamin C per day.

Numerous other clinical trials are underway in China investigating the effect of IV and oral vitamin C. Trials are also underway in a few hospitals in the US. While we wait for more published results, emerging evidence supports the use of vitamin C for COVID-19.

Anti-Viral Effects: Hydroxychloroquine and Zithromax

Chloroquine and its cousin hydroxychloroquine, are medications that have been used for decades to treat malaria all over the world. Previous studies done in the early 2000s, demonstrated that chloroquine active against the SARS-CoV virus that caused the SARS outbreak in 2003.

Just recently two studies (3, 4) have confirmed that both chloroquine and hydroxychloroquine effectively inhibit the SARS-CoV-2 virus responsible for current COVID-19 pandemic.

These anti-malarial medications are now being highly considered for treating COVID-19 patients. Although data from human studies is currently limited at this time a number of clinical trials investigating these antimalarial medications are underway.

A recent study from France investigated the impact of hydroxychloroquine alone and in combination with azithromycin, a common antibiotic on viral clearance in patients with COVID-19.

Twenty two COVID-19 positive patients received 200 mg of hydroxychloroquine three times per day for ten days. Among these, six patients were treated with azithromycin (500 mg on day one and 250 mg daily for four days) to prevent bacteria super infections. Sixteen COVID-19 patients did not receive therapy and served as a control group. PCR based tests to detect viral loads were performed throughout the study period.

Significant reduction in viral loads of COVID-19 patients after being treated with hydroxychloroquine alone and when combined with azithromycin.

Although the trial has not ended their results show significant reduction in viral loads of COVID-19 patients after being treated with hydroxychloroquine alone and when combined with azithromycin.

70% of patients who only received hydroxychloroquine tested negative for SARS-CoV-2 at day 6 of treatment compared to 12.5% in the control group. At day 6 of treatment, 100% of patients treated with both hydroxychloroquine and azithromycin tested negative for SARS-CoV-2.

Protection Against COVID-19 with Stem Cells and Exosomes

Stem cells have long been used in studies as an emerging therapy for lung disease such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and pneumonia.

Recently, they have been identified as a potentially effective treatment option for COVID-19 due to their anti-inflammatory, immune modulatory and tissue repair properties. In fact, two clinical trials (1, 2 ) from China have already demonstrated promising results of intravenous stem cells in moderate and severe COVID-19 cases.

Stem cells along with exosomes may also be useful for COVID-19 prevention. Stem cells have been shown to support the immune system by improving the function of specific anti-viral immune cells as well as reducing an overactive immune response.

Stem cell therapy is also beneficial for many of the underlying health conditions such as heart, lung and kidney disease and may reduce the risk of severe COVID-19 cases and death.

Exosomes, which share many of the therapeutic properties of stem cells, may also be beneficial. In animal studies, exosomes have been shown to inhibit viral replication of the influenza virus, significantly reduce viral shedding and reduce lung damage.

Although there are no clinical trials showing its efficacy in COVID-19, a trial for inhaled exosomes is underway in China and a New Jersey doctor recently reported significant improvement in a COVID-19 patient with acute respiratory distress syndrome (ARDS) after being treated with exosomes.

Considering SARS-CoV-2 has a number of mechanisms to evade the immune system priming it with natural agents and advanced therapies may be a promising strategy for prevention of COVID-19.


Conclusion

In addition to the commonly recommended strategies to prevent COVID-19 infection additional measures to support the immune system should be taken, considering that most people in the US are likely to be exposed to SARS-CoV-2 over the next 12 months. Vitamins and minerals including vitamin D, vitamin A, and zinc, along with other natural agents such as curcumin, resveratrol, alpha lipoic acid, melatonin, mushrooms and probiotics may be useful. In addition, stem cells and exosomes may exert added benefit for the prevention of COVID-19.

SOURCES:

Devin Wilson, ND

NaturopathiC Doctor

Visit Dr. Devin Wilson at Valley Integrative Health