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Ivermectin and CV19

May 7th, 2021

By Will Block

Given all the COVID-19 suffering, the promise for relief, and the growing vaccine side-effects, is it any wonder that a fervent search for other drugs and supplements is growing?

Dr. Ryan Cole, the CEO/ Medical Director of Cole Diagnostics, an independent IDAHO lab, may have some answers. Dr. Cole has seen over 350,000 patients in his career and conducted over 100,000 COVID-19 tests.

Dr. Cole has this to say about vitamin D3 (hereafter named as vitamin D):

  • Coronavirus infections are seasonal.
  • In reality, there are only low vitamin D seasons.
  • Inflammatory (cytokine storms), are present in all COVID-19 cases and cannot be controlled without adequate vitamin D levels.
  • Massive numbers of Americans have low vitamin D levels.
  • 96% of ICU patients are vitamin D deficient.
  • You cannot synthesize vitamin D from sunlight during fall and winter at 35-degrees north and above.
  • If you live in northern climates, you are immune suppressed if you do not supplement with vitamin D during fall and winter.
  • Scandinavian countries (Finland, Norway, Sweden, Denmark) test their citizens twice a year for vitamin D and fortify 35 foods with vitamin D.
  • But our population is left vulnerable to any seasonal viral infection- without a public health program to promote vitamin D adequacy.
  • There is not social disparity of care, but darker skin pigmentation which inhibits sunshine vitamin D synthesis in the skin.
  • Fauci says he personally takes 8,000-9,000 units of vitamin D per day. Why has this has not become a public health message?
  • The top three public health messages should be:
  1. vitamin D
  2. vitamin D
  3. vitamin D

 

Ivermectin Arrives

Ivermectin fits the treatment bill. Four billion doses of Ivermectin have safely been taken. Of the half million COVID-19 deaths in North America, there would be 375,000 less deaths if Ivermectin were administered! Public health officials may have blood on their hands. 100% of Ivermectin treated patients don’t get ill. This works for all genetic variants.

Pre-Covid Cocktail

For patients desiring protection before possible exposure to COVID-19, such as travel into high-risk areas, a combination of Ivermectin, zinc, vitamin C, and vitamin D is recommended as part of the safety plan.

 

Dosages are as follows:

Ivermectin treatment under supervision, is typically being dosed at 0.2 mg per kg bodyweight, each 24-hour period. Another way to calculate your personal treatment dose; divide your body weight in pounds by 33. That’s how many Ivermectin 3 mg tablets you should take in one day. Take that many tabs on days 1, 3, 10, 17, and 25 (one month supply). In addition:

 

Zinc Sulfate         50 mg/daily

Vitamin C            3-5,000 mg/daily

Vitamin D3          4-5,000 IU/daily

 

Ivermectin Enters the Field

Recently, several groups of physicians and multidisciplinary committees have recommended that the Honduran government establish a new public health policy to administer weekly doses of Ivermectin (12 to 18 mg) in the healthy adult population.

 

[Editor’s note: Those with ‘lessor’ concerns, are typically availing themselves of a prophylactic dose of ivermectin as little as 3 mg per week].

 

This is because there are clinical and laboratory study results that justify its use for prophylaxis and to lower the viral load of SARS-CoV-2, which is the virus that causes COVID-19.

The Problem of “Experts”

And the public and the news media always take great comfort that an “expert” gave them this idea based on the “science.”  Trouble is, you can always find another “expert” with equal credentials who will offer a completely contradictory perspective. Also, the Honduran government may not parallel other Latin-American countries, let alone European or SE Asian nations.

 

Ivermectin as a Wonder Drug

Ivermectin proposes SO many potential effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties that it has been referred to as a wonder drug.1 It is highly effective against many microorganisms including some viruses.

In a recent comprehensive systematic review, the antiviral effects of Ivermectin appear to work on RNA viruses such as Zika, dengue, yellow fever, West Nile disease, etc.

Inflammation is an intrinsic defense mechanism triggered by the immune system against infection or injury. Chronic inflammation allows the host to recover or adapt through cellular and humoral responses, whereas acute inflammation leads to cytokine storms, which can result in tissue damage.

In a recent review, the paper presented the overlapping outcomes of cancer inflammation with virus-induced inflammation.2 The study emphasizes how anti-inflammatory drugs that work against cancer inflammation may ALSO work against the inflammation caused by the COVID-19 viral infection.

 

 

FDA Prevails … In Error

The FDA does not approve Ivermectin for COVID-19, owing to a variety of possible side-effects. Ha! But this does not include vaccines, which ironically are proving to have many potentially harmful side effects, including blood clots for AstraZenica’s vaccine.

While cancer remains second among the diseases associated with mortality worldwide, cancer patients’ mortality rates are often observed over extended periods after illness, usually ranging from months to years. However, the mortality rates associated with COVID-19 disease are robust.

Overlapping Inflammatory Mechanisms

Since both cancer and COVID-19 disease share overlapping inflammatory mechanisms, repurposing some anticancer and anti-inflammatory drugs for COVID-19 may lower mortality rates. Here, are reviewed some of these inflammatory mechanisms. Also, the researchers propose some potential chemotherapeutic agents to mediate in them.3

Also studied are the repercussions of anti-inflammatory drugs such as glucocorticoids and hydroxychloroquine with zinc or antiviral drugs such as Ivermectin, against SARS-CoV-2 induced cytokine storm.

Ivermectin Treats COVID-19

A new double-blind study has determined that Ivermectin is an efficacious treatment for mild COVID-19.4 Conducted in Cali, Colombia, the study participants were identified by simple random sampling from the state’s health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled during mid-2020 and followed up through December 21, 2020.

Patients were randomized to receive Ivermectin, 300 μg/ kg of body weight per day for 5 days (n=200) or placebo (n=200). The Primary outcome was the time to resolution of symptoms within a 21-day follow-up period. Adverse events were also collected.

The median time to resolving of symptoms was 10-days in the Ivermectin group compared with 12 days in the placebo group. By day 21, 82% in the Ivermectin group and 79% in the placebo group had resolved symptoms.

 

Comparative Effectiveness

There is an urgent need for effective treatments to prevent or attenuate lung and systemic inflammation, endotheliitis, and thrombosis related to COVID-19. 5

The aim of yet one more study was to assess the effectiveness of a multidrug-therapy consisting of Ivermectin, Azithromycin, Montelukast and Acetylsalicylic Acid (“TNR4” therapy) to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico.6

A comparative effectiveness study was performed among 768 confirmed SARS-CoV-2 cases aged 18 to 80 years, who received ambulatory care at the Ministry of Health of Tlaxcala, Mexico. A total of 481 cases received the TNR4 therapy, while 287 received another treatment (comparison group). All participants received home visits and/or phone calls for clinical evaluation during the 14 days after enrollment.

Nearly 85% of cases who received the TNR4 recovered within 14 days compared to 59% in the comparison group. Likelihood of recovery within 14 days was 3.4 times greater among the TNR4 group than in the comparison group.

Patients treated with TNR4 had a 75% and 81% lower risk of being hospitalized or death, respectively than the comparison group. TNR4 therapy improved recovery and prevented risk of hospitalization and death among ambulatory COVID-19 cases.

 

High Compound Library Screen

In FDA-approved studies for parasitic indications, Ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral.6-7 Researchers first identified Ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer.

Ivermectin demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins.

Cell culture experiments have shown strong antiviral action towards a range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (which causes COVID-19).

Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit.

There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency-use authorized drugs do not result in significant and widespread patient improvement.

The FDA-approved drug Ivermectin has long been shown to be both an antihelmintic agent, (a group of antiparasitic drugs that expel parasitic worms [helminths]) and a potent inhibitor of viruses such as Yellow Fever Virus.

 

More Potent Therapeutic Antiviral Dose

In a current study, Ivermectin is packaged as an orally administrable nanoparticle that could serve as a vehicle to deliver a more potent therapeutic antiviral dose. It could also demonstrate efficacy to decrease expression of viral spike protein and its receptor angiotensin-converting enzyme 2 (ACE2), both of which are keys to lowering disease transmission rates.

The study also reports that the targeted nanoparticle delivered Ivermectin can inhibit the nuclear transport activities mediated through heterodimers as a possible mechanism of action. Moreover, it sheds light on Ivermectin loaded, orally administrable, biodegradable nanoparticles. These can be a potential treatment option for the novel coronavirus through a multilevel inhibition.

As both ACE2 targeting and the presence of spike protein are features shared among this class of virus, this platform technology has the potential to serve as a therapeutic tool not only for COVID-19 but for other coronavirus strains as well.

 

Great Burden to Healthcare Worldwide

 Viruses such as human cytomegalovirus, human papillomavirus (HPV), Epstein-Barr virus, HIV, and SARS-CoV-2, represent a great burden to human health worldwide.8-9 The FDA-approved anti-parasite drug Ivermectin is also an antibacterial, antiviral, and anticancer agent, which offers more potentiality to improve global public health, and it can effectively inhibit the replication of SARS-CoV-2 in vitro.

This study sought to identify Ivermectin-related virus infection pathway alterations in human ovarian cancer cells. Stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics was used to analyze human ovarian cancer cells treated with and without Ivermectin (20 μmol/L) for 24 h, which identified many Ivermectin-related proteins in ovarian cancer cells.

Gene Ontology analysis revealed 10 statistically significant cellular components, 13 molecular functions, and 11 biological processes. These findings demonstrate the broad-spectrum antiviral property of Ivermectin for COVID-19 treatment in the context of predictive, preventive, and personalized medicine in virus-related diseases.

 

Screening Identifies Potentially Effective Drugs

The small molecule macrocyclic lactone Ivermectin, approved by the US Food and Drug Administration for parasitic infections, has received renewed attention in the last eight years due to its exciting potential as an antiviral.10

Astonishingly, cell culture experiments show robust antiviral action towards HIV-1, dengue virus, Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2. This mini-review discusses the case for Ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.

COVID-19 is a critical pandemic that has affected human communities worldwide and (we repeat) there is an urgent need to develop effective drugs.11 Although there are many candidate drug-compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary.

Numerous drugs were successfully screened, including many known antiviral drug compounds such as sorafenib, sorafenib, alvocidib, mitoxantrone, geldanamycin, fluticasone, and quercetin.12

One thing more … COVID-19 is likely mutating and is turning on younger age groups.13

We will continue to report these scientific interventions, missteps, and discoveries with discernment.

 

 

References

1.     Heidaryz F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020 Sep;73(9):5093-602.

  1. Amere Subbarao S. Cancer vs. SARS-CoV-2 induced inflammation, overlapping functions, and pharmacological targeting. 2021 Mar 15, 1-24.
  2. Mamkulathil Devasia R, Altaf M, Alrefaei AF. Manoharadas S. Enhanced production of camptothecin by immobilized callus of Ophiorrhiza mungos and a bioinformatic insight into its potential antiviral effect against SARS-CoV-2. J King Saud Univ Sci. 2021 Mar;33(2):101344.
  3. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun; 178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3. López-Medina E, López P, Hurtado IC, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19: A Randomized Clinical Trial. JAMA. 2021 Mar 4; e213071.
  4. Lima-Morales R, Méndez-Hernández P, Flores YN, et al. Effectiveness of a multidrug therapy consisting of Ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico. Int J Infect Dis. 2021 Feb 9; S1201-9712(21)00100-4.
  5. Jans DA, Wagstaff KM. The broad-spectrum host-directed agent Ivermectin as an antiviral for SARS-CoV-2? Biochem Biophys Res Commun. 2021 Jan 29; 538:163-72.
  6. Surnar B, Kamran MZ, Shah AS, Dhar S. Clinically approved antiviral drug in an orally administrable nanoparticle for COVID-19. ACS Pharmacol Transl Sci. 2020 Dec 1;3(6):1371-80.
  7. Pandey S, Pathak SK, Pandey A, Salunke AA, Chawla J, Sharma A, Sharma S, Thivari P, Ratna HVK. Ivermectin in COVID-19: What do we know? Diabetes Metab Syndr. Nov-Dec 2020;14(6):1921-2.
  8. Li N, Zhao L, Zhan X. Quantitative proteomics reveals a broad-spectrum antiviral property of Ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-75.
  9. Jans DA, Wagstaff KM. Ivermectin as a Broad-spectrum host-directed antiviral: The Real Deal? 2020 Sep 15;9(9):2100.
  10. Taguchi Y-H, Turki T. A new advanced in silico drug discovery method for novel coronavirus (SARS-CoV-2) with tensor decomposition-based unsupervised feature extraction. PLoS One. 2020 Sep 11;15(9): e0238907.
  11. Montoya J, Ugaz C, Alarcon S, et al. COVID-19 in pediatric cancer patients in a resource-limited setting: National data from Peru. Pediatr Blood Cancer. 2021 Feb;68(2): e28610. doi: 10.1002/pbc.28610. Epub 2020 Jul 22.
  12. Danchin A, Turinici G. Immunity after COVID-19: Protection or sensitization? Math Biosci. 2021 Jan; 331:108499. Text 2,788

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