The global COVID-19 pandemic has become a stigma 2020 G. and changed the world of clinical medicine. Initial guidelines for therapeutic behavior were often formulated on the basis of conflicting evidence., but the experience gained at the end of the year allows to rationalize the treatment protocols and to weed out the interventions with a favorable benefit-risk ratio. Simultaneously, the implementation of disease prevention tools remains a largely unmet goal in the pandemic control strategy.. Despite the rapid introduction of the most promising vaccines, problems, caused by the huge number of infected and the rapid spread of the disease, question the search for alternatives to rational, safe and cost-effective prevention.
At the beginning of April this year, An expert panel from Easter at Virginia Medical School in the USA creates and updates a protocol for prevention and treatment of COVID-19, containing a combination of vitamins, minerals, antioxidants and nutrients (Vitamin C, quercetin, zinc, vitamin D., melatonin). In the same month, the Ministry of Health organized a meeting with Acad. Dobrin Svinarov, dmn, and representatives of the specialized pharmaceutical company Natstim EOOD, which is entrusted with the creation of a specialized product, allowing convenient and economically cost-effective application of the proposed protocol in our country, with the main focus on prevention of health professionals on the first line and other contingent with increased risk, as well as for the adjuvant treatment of COVID-19. An expert group of pharmacology specialists was formed, clinical pharmacology and pharmacotherapy, Clinical Laboratory, immunology and pharmaceutical technology (acad. Dobrin Svinarov, dmn - group leader, acad. Bogdan Petrunov, dmn; prof. Rahamin Shekerdzhiyski, dfn; prof. Georgi Momekov, dfn), which conducted an in-depth review of the literature data and together with the development and technical team of Natstim Ltd. created the product "Virus Safe + Melatonin, whose composition is summarized in Table 1. The expert group also developed a protocol for the simultaneous application of Virus Safe + Melatonin in combination with Respistim Plus, a new generation of vitamin complex, minerals, antioxidants and immunomodulatory composition of lipopolysaccharides and lipopeptides, in view of the expected synergy, with excellent tolerability.
An increasing number of randomized and observational studies have shown the effectiveness of the individual components in the context of Covid-19., which confirms the rationality of this approach to prevention. Until this message is compiled, Help in PubMed (NIH-NLM) found 597 publications, dedicated to the vitamin C link, quercetin, zinc, vitamin D and melatonin with COVID-19 separately, which 325 for vitamin D., but none, considering the possibility of combining them into one product.
table 1. Qualitative and quantitative composition of “Safe virus + Melatonin”*
| Ingredients | IN 1 tablet | At the maximum daily dose of 3 pills |
|---|---|---|
| Vitamin C | 333,0 mg | 999,0 mg |
| Quercetin | 200,0 mg | 600,0 mg |
| Zinc (such as zinc acetate) | 8,3 mg | 24,9 mg |
| Vitamin D3 (cholecalciferol) | 30,0 μg (1200 IU) | 90,0 μg (3600 IU) |
| Melatonin | 1,8 mg | 1,8 mg |
Brief overview of pharmacological properties and clinical data for the individual components
Vitamin C
As a major component of water-phase antioxidant protection, in infectious diseases, vitamin C is necessary for the normal function of neutrophils. It has been found, that accumulates in macrophages, responsible for T cell maturation and optimal phagocytic activity. In viral infections, increased metabolism of ascorbic acid is found, reduction of the circulating levels and respectively - pronounced deficit. Vitamin C exerts pleiotropic immunomodulatory activity, by enhancing interferon production, reduces cytokine-induced organ damage and promotes the recycling of oxidized endogenous and exogenous antioxidants, including. quercetin, enhancing their antiviral effects. This mechanism helps to suppress the "cytokine storm", causing complicated and severe course of COVID-19. Vitamin C reduces the duration of the symptomatic period and is used in high parenteral doses for the treatment of virus-associated acute respiratory distress syndromes., including COVID-19, as an integral part of the therapeutic protocol.
Quercetin
Quercetin is a natural flavonoid that has a beneficial effect on microcirculation, integrity, smooth muscle tone and barrier functions of blood vessels. It is contained in high concentrations in fruits and vegetables and is considered a major component, determining the cardiovascular protective effect of the "Mediterranean" diet. It acts as an antioxidant and scavenger of free radicals, has a well-defined anti-inflammatory activity, inhibits platelet aggregation, lipid peroxidation and biosynthesis of lipid inflammatory mediators, such as prostaglandins, levkotrieni and others., and also affects important signaling pathways with respect to inflammatory processes and systemic responses to infection. One of its main metabolites stimulates the activity of the nasal ciliated epithelium and enhances mucociliary clearance. The antiviral properties of quercetin are also due to its ability to block the virus from entering the cell and inhibit key enzymes., engaged in viral replication. It is an integral part of the therapeutic protocol for COVID-19.
Zinc
Zinc ions (Zn) have the potential to reduce the risk of viral infections, including SARS-CoV-2, and reduce the duration and severity of the disease. Zn inhibits viral RNA polymerase and favorably modulates the activity of angiotensin-converting enzyme - the cellular receptor of the virus. It also modifies the host response, as it is a cofactor of many enzymes and affects a wide range of physiological functions, including - strengthening of the enzymatic antioxidant protection. Zn decreases cell membrane permeability and transcapillary transport, which helps to reduce local swelling, inflammation and exudation, and their deficiency adversely affects humoral and cellular immunity with an increased risk of infections. Zn deficiency is often asymptomatic and can be detected only by disease provocation of the immune system.. A pronounced correlation was found between Zn levels and COVID-19 output: admission deficiency correlates with poorer clinical course, longer patient stabilization time and higher mortality. Low Zn levels favor viral replication in SARS-CoV2-infected cells. Therefore, Zn supplementation is an integral part of the prophylaxis and treatment protocols for COVID-19.
Vitamin D
Vitamin D reduces the risk of viral and bacterial infections by several mechanisms - affects the barrier functions of target tissues, non-specific immunity, the adaptive immune response, modulates the production and secretion of cytokines, and suppresses the cytokine storm. Vitamin D deficiency is associated with the manifestations of acute respiratory distress syndrome, heart failure and other diseases of degeneration. Vitamin D deficiency activates the renin-angiotensin system (RAAS), which can lead to cardiovascular pathology and adversely affect lung function. Vitamin D blocks SARS-CoV-2-mediated activation of RAAS, complement, the kallikrein-kinin system, blood clotting and fibrinolysis and significantly reduces the release of bradykinin, which causes capillary vasodilation, extravasation and filling of the lung alveoli with the gel visible as "frosted glass", blocking gas exchange. Many studies support the role of vitamin D in reducing the risk of COVID-19 morbidity and mortality. COVID-19 prevention and treatment protocols include vitamin D and its products with very promising results - e.g., randomized use of calcifediol (25-OH-vitamin D.) in hospital treatment significantly reduces the severity of the manifestations, the need for intensive treatment and mortality.
Melatonin
Melatonin, secreted by the pineal gland makes up about 5% of the total content in the body. The remaining amount is synthesized in the mitochondria, is not released into the circulation, and is utilized by the producing cells. Melatonin has hormone functions, neurotransmitter, antioxidant and immune regulator. In case of insufficient synthesis, especially in the third age, a deficit arises with corresponding consequences. The use of melatonin for the prevention and treatment of viral infections, including COVID-19, is based on its powerful antioxidant and immunoregulatory effects and excellent safety profile.
Dosage, biopharmaceutical and pharmacokinetic considerations for Safe Virus
The dosage form and method of administration - sucking or chewing of the tablet core implies a longer stay in the oral cavity and respectively significant local tissue saturation with a simultaneous increase in systemic bioavailability.. Melatonin is included in the form of controlled release tablets, which optimizes the pharmacokinetic properties and safety profile. Other benefits of Virus Safe are reduction of tablet load and improvement of economic profitability, as the application of the original protocol of the Eastern Virginia School of Medicine would require daily intake of five or more dosage units of different products at a much higher cost.
Grounds for combination with Respistim Plus
The expert group considers it very appropriate “Virus safe + Melatonin” to be used in combination with the product “Respist plus” for the most complete, although non-specific antiviral prophylaxis and treatment support for COVID 19. “Respist plus” is a unique combination of multivitamins, trace elements and a complex of membrane lipopolysaccharide and lipopeptide components of bacteria, which cause respiratory infections. In particular, the optimal content of vitamins A and E enhances lipid-phase antioxidant protection; higher pantothenic acid content – antibody formation; trace elements Se, Mn, Cu and Zn – the enzymatic antioxidant protection of the cell; bacterial lipopolysaccharide and lipopeptide components are well-studied means of prevention against the superposition of bacterial infectious complications. Through the bacterial complex contained in Respistim Plus, the most powerful polyvalent immunomodulator, the mechanisms of natural immunity are activated - phagocytosis, surfactant, secretory immunoglobulin A, interferon and toll-like rehearsal.