Safe&Prosper protocol \V/_

Critical Analysis Of The Lifecycle of SARS-CoV-2 For The Development Of Practical Methodologies In The Prevention & Treatment Of COVID-19

The SARS-CoV-2 virus which causes COVID-19 has been shown to exhibit multi-stage effects on the body and its functioning. Rapid research and analysis of symptoms and patient outcomes are now bringing to light how this lifecycle works, possible markers that correlate closely with deficiencies common to primary comorbidities in patients with severe outcomes,  and in turn practical approaches to therapies across each phase of infection.

Evidence based understanding of possible treatments. 

Early indications from studies conducted on SARS-CoV 2 in combination with existing empirical findings established from decades of research in previous outbreaks and studies both in vitro and in vivo informed a practical approach to chemoprophylaxis and early post exposure treatment to effectively limit the ability of the virus to infect as well as inhibit transmission.

In following this methodology, the population will still be exposed to the virus, thus promoting the speed at which herd immunisation levels can be reached in the population. To facilitate ‘safe’ exposure to the virus whilst effectively limiting its ability to cause severe infection, replication, repackaging and transmission, a set of therapies need to be introduced that is affordable, widely available and an acceptable level of tolerance in a wide population set.

The S&P Protocol\V/_

Stage 1 - Risk Of Exposure & Infection

Coronaviruses (CoVs) are enveloped, plus-strand RNA viruses belonging to the family

coronavirus family in the order of Nidovirales. SARS-CoV-2 has many common features with the Coronavirus family thus there are common underlying mechanisms.

Coronavirus delivery of virus particles into the host cell requires binding of the virus to cellular receptors followed by a clathrin-mediated endocytosis to create a viral endosome. This process is mediated by a viral surface glycoprotein termed Spike, a homotrimer of S proteins, binding to the type I integral membrane receptor angiotensin-converting enzyme-2 (ACE2). These receptors are expressed at high levels in type I and II alveolar cells in the lungs but are also found in the heart, kidneys, intestines and the rest of the respiratory tract.

Stage 1 - Pre-Infection Prophylaxis

With rapid spread of the pandemic, huge portions of the world's population are at risk of exposure, with higher segments such as frontline healthcare workers, the elderly, people and those with pre-existing conditions and vitamin deficiencies being most susceptible to infection.

To effectively shield this population from infection, several measures should be taken according to current level of health and respective susceptibility to infection. This necessitates optimisation of vitamin intake to strengthen the immune system: 

Vitamin C is well documented in its ability to improve immune response to infections. Vitamin C affects the function of phagocytes, transformation of T lymphocytes and production of interferon. In particular, vitamin C increases the resistance of chick embryo tracheal organ cultures to infection caused by the coronavirus.

There are several mechanisms by which vitamin D activity is critical for immune defence: vitamin D acts to maintain tight junctions, promote the effect of antimicrobial peptides (i.e., cathelicidin and defensins), and moderate the inflammatory response.

Vitamin D deficiency has been demonstrated to have an exponentially negative effect on the rate of Co-morbidity in those infected with the virus (10x for <20ng/ml). The risk of vitamin D deficiency has been exacerbated by extended ‘shelter in place’ orders around the world.

Inhibiting Viral Membrane Fusion & Endocytosis - HCQ 

“To show an effect you really have to treat early, I don’t know any drug that works better late in infection.” Giving a drug before exposure is as early as it gets.” - Matthew Frieman, Virologist of the University of Maryland School of Medicine.

Many viruses, including SARS-CoV, acidify endosomes in order to breach the cell membrane, release their genetic material and begin replication. Raising the endosomal pH of cell walls using a weak base such as Hydroxychloroquine prophylactically has been shown to interfere with the glycosylation of SARS-CoV-2, which limits the ability for SARS-CoV-2 spike proteins plugging into angiotensin-converting enzyme 2, or ACE2 receptors. 

Sialic acid linked to glycoproteins and gangliosides is also used by many viruses as a receptor for cell entry. HCQ inhibits quinone reductase-2 by binding to sialic acids which also helps to  prevent its spike proteins from gaining entry via these receptors thereby offering additional protection against infection. 

The safety of Hydroxychloroquine has been noted by the WHO, stating the hundreds of millions of doses have been administered worldwide of the past few decades. Prophylaxis requires low dosages that effectively negate the chance of adverse side effects in almost all cases.

Further confirmation of the efficacy of low dose HCQ prophylaxis has been evidenced in Italy. SIR interrogated 1,200 rheumatologists throughout Italy to collect statistics on infections. Out of an audience of 65,000 chronic patients (Lupus and Rheumatoid Arthritis), who systematically take Plaquenil / hydroxychloroquine, only 20 patients tested positive for the virus. Nobody died, nobody is in intensive care, according to the data collected so far.

Stage 2 - Incubation & Viral Replication

Once internalised the fusion of virus with lysosomes depends on a low endosomal and lysosomal pH. Cathepsin B and L activity are inhibited by an elevated endosomal pH. Viral entry into the cytoplasm is likewise dependent on an acidic endosomal pH.

Once released into the cytosol, the virus utilizes a viral RNA-dependent RNA-polymerase (i.e. Replicase) to drive the viral replication, create virions for exocytosis, and thus further the infection of neighboring cells and transmit to the newly repackaged viral cells to other people. An individual viral particle called a virion is able to produce about a million new virions once inside a cell. Studies have shown that this pre-symptomatic replication stage exhibits the highest levels of viral shedding whereby hosts are the most likely to infect other people.

Pulmonary Scarring visible in scans of asymptomatic individuals, this is an unknown characteristic for the future. 

Stage 2 - Asymptomatic Antiviral Therapy

Given that viruses are intracellular parasites that hijack cellular processes to replicate a virus’s genetic material, it is essential antiviral agents have the ability to enter cells. 

Hydroxychloroquine, even at prophylactic dosages, has far reaching abilities for distribution throughout the human body, including entering cells. In doing so, it has been proven to inhibit both viral RNA replication and repackaging functions inside cells by decreasing the acidity of the cytoplasmic environment within key structures such as the endoplasmic reticulum and the golgi apparatus.

In addition, Zinc is able to effectively block virus RDRP (RNA-dependent RNA polymerase) replication of RNA through limiting its engagement with ribosomes by binding with these enzymes. 

It is critical for zinc to be able enter cells to destroy the virus, which makes the discovery of an ionophore as important as zinc’s primary role in infection control. Hydroxychloroquine has been previously identified as an effective zinc ionophore which creates passageways for Zinc to penetrate cell walls.

The combination of these two agents acting together delivers a very powerful antiviral effect, prohibiting viral loads from escalating to the point of patients needing hospitalisation and importantly, from being able to be repackaged for transmission to new hosts. 

Stage 3 - Symptomatic Phase 

Previous studies on Human Coronavirus (HCoV-HKU1) indicate that infection of alveolar cells is associated with the surface expression of viral spike protein, mediating membrane fusion with neighbouring cells leading to syncytium formation. This allows direct cell to cell spread of virus which could play a role in the pathogenesis of lung disease and immune system evasion.

Early symptoms mainly affect the upper respiratory tract, although increasing evidence is showing the scarring, bilateral ground-glass opacity is already presenting in the lungs of the infected. 

When patients start to present symptoms of COVID-19, they have varied greatly across regions which is an indication of possible mutations of the virus. Younger, healthier people have a reasonable chance of recovering in an outpatient setting however those with pre-existing conditions have a much higher susceptibility to progressing to more severe conditions which require hospitalisation.

Stage 3 - Symptomatic Treatment 

The symptomatic stage of infection has been the major focus for suggested therapeutic protocols promoted globally thus far. There is growing consensus that immediate treatment with the combination of Hydroxychloroquine, Azithromycin (Raoult) + Zinc (Zelenko) are  the best options for treatment at this stage of infection.

Supplementation with Vitamin C helps the epithelial layer in the respiratory tract to combat the virus and prevent rapid inflammation due to immune response to the increasing stress from the infection. 

The later this treatment is started the lower the beneficial effects of the Hydroxychloroquine and Zinc therapy will be, the Azithromycin is well documented for its ability to clear ENT infections as well as assisting in clearing the lungs from mucus build up from pneumonia like symptoms which develop with acute cases.

Starting therapy with Hydroxychloroquine at this stage is likely too late to assist through its antiviral effects, however if treatment has been started earlier, ideally Stage 1, the immunomodulatory effects of the medicine will help to subdue the onset of the cytokine storm which has been shown to lead to respiratory failure.

Another beneficial effect of Hydroxychloroquine is its ability to limit blood coagulation which is another acute symptom of late stage SARS-CoV-2 infection which is being found throughout patients major organs.

Vitamin C is proving highly beneficial at this final stage of infection with intravenous  administration of very high dosages to ICU patients. 

Zinc is a vital component that limits the build up of superoxide by assisting the ACE2 receptors in the conversion of AT-11 to AT1-7. This process needs support as it becomes increasingly difficult with the increased number of ACE2 receptors being compromised by SARS-COV-2 S-proteins attaching themselves to the cells in the lungs.

The Safe & Prosper Protocol \V/_

Recommended Treatment Per Stage:

#SnPprotocol #PreExposureProphylaxis

1- Hydroxychloroquine 400mg load dose, then 200mg once a week

2- Zinc sulphate 40mg once a day

3- Supplement with Vitamin C & D at daily recommended nutritional dosages

#SnPprotocol #PostExposureProphylaxis

1- Hydroxychloroquine 400mg once a week

2- Zinc sulphate 40mg once a day

3- Supplement with Vitamin C & D at daily recommended nutritional dosages

Stage 3 Symptomatic Therapy:

Professor Raoult Protocol + Zelenko Protocol

+ supplement with Vitamin C & D at daily recommended nutritional dosages

MacKenzie&Greeff