ZIKA VIRUS: Experimental therapy.

Dmitri Popov. PhD, Radiobiology. MD (Russia)

Advanced Medical Technology and Systems Inc. Canada. intervaccine@gmail.com

ZIKA VIRUS: Experimental therapy.• Research Proposal: ZIKA VIRUS: Experimental therapy.• Dmitri Popov• Full-text · Research Proposal · Feb 2016• File name: ZIKAEXPEERIMENTALTREATMENT.pptx

DOI: 10.13140/RG.2.1.3462.8888• http://www.slideshare.net/dlpopov

ZIKA VIRUS: Experimental therapy.• Genus Flavivirus (type species Yellow fever virus, others include

West Nile virus, Dengue Fever and Zika virus)—contains 67 identified human and animal viruses.• Flaviviridae have monopartite, linear, single-stranded RNA genomes

of positive polarity, 9.6 to 12.3 kilobase in length. The 5'-termini of flaviviruses carry a methylated nucleotide cap, while other members of this family are uncapped and encode an internal ribosome entry site.• https://en.wikipedia.org/wiki/Flaviviridae

ZIKA VIRUS: Experimental therapy.• Viral replication is cytoplasmic. Entry into the host cell is achieved

by attachment of the viral envelope protein E to host receptors, which mediates clathrin-mediated endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method of transcription. Translation takes place by viral initiation. The virus exits the host cell by budding. Humans and mammals serve as the natural host. The virus is transmitted via a vector (ticks and mosquitoes)• https://en.wikipedia.org/wiki/Flaviviridae

ZIKA VIRUS: Experimental therapy.• Major diseases caused by the Flaviviridae family include:• Dengue fever• Japanese encephalitis• Kyasanur Forest disease• Murray Valley encephalitis• St. Louis encephalitis• Tick-borne encephalitis• West Nile encephalitis• Yellow fever• Hepatitis C Virus Infection• Zika Virus• https://en.wikipedia.org/wiki/Flaviviridae

ZIKA VIRUS: Experimental therapy.• Clinical features and sequelae The incubation period ranges between

approximately three to 12 days after the bite of an infected mosquito. Most of the infections remain asymptomatic (approximately 80%). Disease symptoms are usually mild and the disease in usually characterised by a short-lasting self-limiting febrile illness of 4–7 days duration without severe complications, with no associated fatalities and a low hospitalisation rate. The main symptoms are maculopapular rash, fever, arthralgia, fatigue, non-purulent conjunctivitis/conjunctival hyperaemia, myalgia and headache. The maculopapular rash often starts on the face and then spreads throughout the body. Less frequently, retro-orbital pain and gastro-intestinal signs are present. - See more at: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx#sthash.XS0XOOGV.dpuf

ZIKA VIRUS: Experimental therapy.• Congenital central nervous system malformationsmalformations such as

microcephaly in foetuses and newborns from mothers possibly exposed to Zika virus during pregnancy were notified during recent Zika disease outbreaks (French Polynesia and Brazil). Unusual increases of Guillain–Barré syndrome were reported in several countries in the Americas and French Polynesia coinciding with the Zika virus outbreak.

•Further evidence is needed to establish a causal link between Zika virus infection and these neurological/neurodevelopmental impairments or auto-immune conditions.

• - See more at: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx#sthash.XS0XOOGV.dpuf

ZIKA VIRUS: Experimental therapy.• Diagnostics Zika virus disease diagnostics is primarily based on detection of viral

RNA from clinical specimens in acutely ill patients. The viraemic period appears to be short, allowing for direct virus detection during the first 3–5 days after the onset of symptoms. Zika virus RNA has been detected in urine up to 10 days after onset of the disease. From day five post onset of disease, serological investigations can be conducted by detection of Zika-specific IgM antibodies and confirmation by neutralisation, seroconversion or four-fold antibody titer increase of Zika specific antibodies in paired serum samples. Serological results should be interpreted according to the vaccination status and previous exposure to other flaviviral infections. - See more at: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx#sthash.XS0XOOGV.dpuf

ZIKA VIRUS: Experimental therapy.• Case management and treatment There is no vaccine or specific

prophylactic treatment. Differential clinical diagnostic should be considered as well as co-infection with other mosquito-borne diseases such as dengue fever, chikungunya and malaria. The treatment is symptomatic and mainly based on pain relief, fever reduction and anti-histamines for pruritic rash. Treatment with acetylsalicylic acid and no-steroidal anti-inflammatory drugs was discouraged because of a potential increased risk of haemorrhagic syndrome reported with other flaviviruses as well as the risk of Reye's syndrome after viral infection in children and teenagers. - See more at: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-health-professionals/Pages/factsheet_health_professionals.aspx#sthash.XS0XOOGV.dpuf

ZIKA VIRUS: Experimental therapy.•There is no vaccine or specific prophylactic treatment.•So, looks like any therapy for treatment ZIKA virus does not exist.•What we can do?

ZIKA VIRUS: Experimental therapy.• Experimental therapy include treatment of viremia with chlorine

containing oxidizers.• Chlorine? Oxidizers?• Bleach?• Not possible?• Could be harmful?

ZIKA VIRUS: Experimental therapy.• Chlorine containing oxidizers?• What is it?• http://www.flochem.com/msds/2014/FloChem-SodiumHypochlorite-MSDS.pdf• http://www.environmental-expert.com/Files%5C5306%5Carticles%5C13867%5C501.pdf• In chemistry, hypochlorite is an ion composed of chlorine and oxygen, with the chemical formula

ClO−. It can combine with a number of counter ions to form hypochlorites, which may also be regarded as the salts of hypochlorous acid. Common examples include sodium hypochlorite (household bleach) and calcium hypochlorite (bleaching powder, swimming pool "chlorine").

• Hypochlorites are frequently quite unstable in their pure forms and for this reason are normally handled as aqueous solutions. Their primary applications are as bleaching, disinfection and water treatment agents but they are also used in chemistry for chlorinationand oxidation reactions.

• https://en.wikipedia.org/wiki/Hypochlorite

ZIKA VIRUS: Experimental therapy.• The human immune system generates minute quantities of

hypochlorite during the destruction of pathogens. This takes place within special white blood cells, called neutrophil granulocytes; which engulf viruses and bacteria in an intracellular vacuole called the phagosome, where they are digested. Part of the digestion mechanism involves an enzyme-mediated respiratory burst, which produces reactive oxygen-derived compounds, including superoxide (which is produced by NADPH oxidase). Superoxide decays to oxygen and hydrogen peroxide, which is used in a myeloperoxidase-catalysed reaction to convert chloride to hypochlorite.

ZIKA VIRUS: Experimental therapy.• So, hypochlorite is a natural product for human organism, and

elaborated by immune cells for protection against infection.• Harrison, J. E., and J. Schultz (1976). "Studies on the chlorinating

activity of myeloperoxidase". Journal of Biological Chemistry 251 (5): 1371–1374. PMID 176150.• Jump up^ Thomas, E. L. (1979).

"Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: Nitrogen-chlorine derivatives of bacterial components in bactericidal action against Escherichia coli". Infect. Immun. 23 (2): 522–531. PMC 414195. PMID 217834.

ZIKA VIRUS: Experimental therapy.• The choice of an irrigating solution for use in infected root canals requires previous

knowledge of the microorganisms responsible for the infectious process as well as the properties of different irrigating solutions. Complex internal anatomy, host defenses and microorganism virulence are important factors in the treatment of teeth with asymptomatic apical periodontitis. Irrigating solutions must have expressive antimicrobial action and tissue dissolution capacity. Sodium hypochlorite is the most used irrigating solution in endodontics, because its mechanism of action causes biosynthetic alterations in cellular metabolism and phospholipid destruction, formation of chloramines that interfere in cellular metabolism, oxidative action with irreversible enzymatic inactivation in bacteria, and lipid and fatty acid degradation. The aim of this work is to discuss the mechanism of action of sodium hypochlorite based on its antimicrobial and physico-chemical properties.

• http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• Sodium hypochlorite is recommended and used by the majority of

dentists because this solution presents several important properties: antimicrobial effect , tissue dissolution capacity and acceptable biologic compatibility in less concentrated solutions. In relation to antimicrobial effect, studies have shown that sodium hypochlorite decreases microorganism number during the treatment of teeth with apical periodontitis .• http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• Estrela (16) studied the efficacy of root canal irrigating solutions (1, 2 and

5% sodium hypochlorite, 2% chlorhexidine digluconate, 1% calcium hydroxide, and HCT20, a solution of calcium hydroxide associated with a detergent) on S. aureus, E. faecalis, P. aeruginosa, B. subtilis, C. albicans and a mixture of these microorganisms. The purpose was to determine the minimum inhibitory concentration of the tested solutions with a serial dilution in the proportion of 1:10, and antimicrobial activity with direct exposure at 5, 10, 15, 20 and 30 min. It was concluded that the minimum concentration of 1% sodium hypochlorite required for inhibiting S. aureus, E. faecalis, P. aeruginosa and C. albicans was 0.1%, and 1% for B. subtilis and for the mixture. http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• All microorganisms were inactivated by this solution at all experimental periods (5,

10, 15, 20 and 30 min). The minimum concentration of 2% sodium hypochlorite required for inhibiting S. aureus, E. faecalis, P. aeruginosa and C. albicans was 0.2%, and 2% for B. subtilis and for the mixture. All microorganisms were inactivated by this solution at all experimental periods. The minimum concentration of 5% sodium hypochlorite required for inhibiting all microorganisms was 0.5%, at all time periods. Chlorhexidine digluconate (2%) showed minimum inhibitory concentration of 0.000002% for S. aureus, 0.002% for P. aeruginosa, 0.02% for E. faecalis, B. subtilis, C. albicans and the mixture. Antimicrobial effectiveness in the direct exposure test was observed at all experimental periods for S. aureus, E. faecalis and C. albicans, but it was ineffective for P. aeruginosa, B. subtilis and for the mixture at all periods. http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• Sodium hypochlorite presents high surface tension (75 dynes/cm) and

minimum inhibitory concentration lower than 1% for resistant microorganisms (S. aureus, E. faecalis, P. aeruginosa, B. subtilis and C.albicans). The concentration rise is directly proportional to the antimicrobial effect and tissue dissolution capacity and inversely proportional to biologic compatibility. Thus, considering the high surface tension and that antimicrobial action can be achieved with the less concentrated solution, the better option is 1% sodium hypochlorite.• http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• Physico-chemical characteristics of sodium hypochlorite are important

for the explanation of its mechanism of action. The saponification, amino acid neutralization and chloramination reactions that occur in the presence of microorganisms and organic tissue lead to the antimicrobial and tissue dissolution process. The antimicrobial activity is related to bacterial essential enzymatic sites promoting irreversible inactivation by hydroxyl ions and the chloramination reaction. The organic dissolution action can be observed in the saponification reaction when sodium hypochlorite degrades lipids and fatty acids resulting in the formation soap and glycerol. http://www.forp.usp.br/bdj/bdj13(2)/v13n2a07/v13n2a07.html

ZIKA VIRUS: Experimental therapy.• Sodium hypochlorite in higher concentrations is more aggressive

while in lower concentrations (0.5% to 1%), it is biocompatible . For a substance to be biocompatible, it must present no or only a discreet tissue reaction at all periods and moderate or intense tissue reaction at 7 days which decreases in intensity with time until reaching a non-significant tissue reaction.

ZIKA VIRUS: Experimental therapy.• Byströn A, Sundqvist G. Bacteriologic evaluation of the effects of 0.5%

sodium hypochlorite in endodontic therapy. Oral Surg Oral Med Oral Pathol 1983;55:307-312• Estrela CRA. Eficácia antimicrobiana de soluções irrigadoras de canais

radiculares. [Master's thesis]. Goiânia: Federal University of Goiás; 2000. 80p. Internet site: http://estrela.neomundi.com.br/

ZIKA VIRUS: Experimental therapy.• Using a quantitative suspension test method, the antiviral activity of sodium hypochlorite (NaOCl)

and sodium dichloroisocyanurate (NaDCC) against human immunodeficiency virus (HIV) was investigated. Viral suspensions were prepared containing 10(4)-10(5) syncitial forming units ml-1 in 0.9% saline or 0.9% saline containing 10% v/v plasma to simulate clean and dirty conditions. A syncitial inhibition assay on C8166 lymphoblastoid line was used to determine viral titre. Results indicate that satisfactory disinfection (3-4 log reduction in 2 min) can be achieved using NaDCC and NaOCl at concentrations of 50 ppm and 2500 ppm available chlorine (AvCl2) for clean and soiled conditions respectively. For treatment of blood spillages, the addition of NaDCC and NaOCl solutions (10,000 ppm) to equal volumes of contaminated blood (giving a final AvCl2 concentration of 5000 ppm of blood) was sufficient to produce total kill within 2 min. For treatment of spillage material, chlorine-releasing powder formulations--which produce higher AVCl2 concentrations and achieve containment of spillage material--offer an effective alternative.

• J Hosp Infect. 1990 Apr;15(3):273-8.• Evaluation of hypochlorite-releasing disinfectants against the human immunodeficiency virus (HIV).• Bloomfield SF1, Smith-Burchnell CA, Dalgleish AG.

ZIKA VIRUS: Experimental therapy.• The antiviral activities of sodium dichloroisocyanurate (NaDCC) and a commercial product

(Solprogel 2%) against human immunodeficiency virus type 1 (HIV-1) were investigated using a quantitative suspension test method. Solprogel is a compound that contains NaDCC and a biodegradable polymer of acrylic acid. Viral suspensions were prepared containing 3.2 x 10(6) tissue culture infective dose 50 (TCID50) in culture media. Syncytium formation in the MT-2 line and HIV antigen p24 on the supernatant of the cultures were used to determine viral titre. Results indicate that satisfactory disinfection (1000-fold reduction in 5 min) can be achieved using NaDCC and Solprogel at concentrations of 100 and 120 ppm available chlorine, respectively.

• J Hosp Infect. 1996 Nov;34(3):223-8.• Evaluation of the disinfectant effect of Solprogel against human immunodeficiency virus

type 1 (HIV-1).• Hernández A1, Belda FJ, Domínguez J, Matas L, Gimenez M, Caraballo M, Ramil C, Ausina V.

ZIKA VIRUS: Experimental therapy.• Sodium hypochlorite (NaOCl) is the active ingredient in household bleach and is a

very common chemical. It has been used in medical and commercial situations dating back to the 18th century for its disinfectant properties, including topical use in medicine as an antiseptic. For this indication, NaOCl is a proven and safe chemical. However, exposure of NaOCl beyond topical use, whether it is intentional or accidental, is associated with significant risks due to its strong oxidizing properties. • Spectrum of sodium hypochlorite toxicity in man—also a concern for nephrologists• Brandon Peck1, 1 Department of Medicine, Baylor College of Medicine, Houston, TX,

USA, 2 Division of Nephrology, Baylor College of Medicine, Houston, TX, USA and 3 Department of Pharmacy, The Methodist Hospital; Weill Cornell University, Houston, TX, USA

ZIKA VIRUS: Experimental therapy.• “Although NaOCl has extremely low toxicity in the concentrations

used for medical disinfection, it is often sold in concentrated solutions meant for dilution commercially. • At these high concentrations, there is a significant potential

for toxicity. “• Brandon Peck1, 1 Department of Medicine, Baylor College of

Medicine, Houston, TX, USA, 2 Division of Nephrology, Baylor College of Medicine, Houston, TX, USA and 3 Department of Pharmacy, The Methodist Hospital; Weill Cornell University, Houston, TX, USA

ZIKA VIRUS: Experimental therapy.• NaOCl is a chemical compound consisting of sodium, oxygen and

chlorine. It is manufactured using by bubbling chlorine gas into sodium hydroxide (NaOH) to form equal amounts of NaOCl and NaCl. Typical concentrations found in commercial bleach products range between 3 and 5% solution with an approximate pH of 11 . Mixed with water, NaOCl combine to generate highly reactive hypochlorous acid (HOCl), conferring its potent antibacterial and antifungal properties.• Brandon Peck1, 1 Department of Medicine, Baylor College of Medicine,

Houston, TX, USA, 2 Division of Nephrology, Baylor College of Medicine, Houston, TX, USA and 3 Department of Pharmacy, The Methodist Hospital; Weill Cornell University, Houston, TX, USA

ZIKA VIRUS: Experimental therapy.• In the USA, NaOCl is used in the medical profession as a topical

antiseptic in many applications such as burns, ulcers or for cleaning the root canal system in endodontics. When used in this fashion, its toxicity is extremely low, a fact that has been proven with animal models as well as being observed in humans over time.• Brandon Peck1, 1 Department of Medicine, Baylor College of

Medicine, Houston, TX, USA, 2 Division of Nephrology, Baylor College of Medicine, Houston, TX, USA and 3 Department of Pharmacy, The Methodist Hospital; Weill Cornell University, Houston, TX, USA

ZIKA VIRUS: Experimental therapy.• SO, In low concentrations Sodium hypochlorite (NaOCl) effective and safe, at

high concentration Sodium hypochlorite (NaOCl) extremely toxic.• "The dose makes the poison" (Latin: ''sola dosis facit venenum'') is an

adage intended to indicate a basic principle of toxicology. It is credited to Paracelsus who expressed the classic toxicology maxim "All things are poison and nothing is without poison; only the dose makes a thing not a poison." This is often condensed to: "The dose makes the poison" or in Latin "Sola dosis facit venenum". It means that a substance can produce the harmful effect associated with its toxic properties only if it reaches a susceptible biological system within the body in a high enough concentration. https://en.wikipedia.org/wiki/The_dose_makes_the_poison

ZIKA VIRUS: Experimental therapy.• Can we use low dose, nontoxic Sodium hypochlorite (NaOCl) for I/V

therapy of infections diseases?

ZIKA VIRUS: Experimental therapy.• Разрешение Фармкомитета МЗ СССР N 418 от 13.04.91).• Approved by National Pharmaceutical Department. Ministry of Public

Health. Russia• Approved for I/V therapy of infections.• Sodium hypochlorite (NaOCl).

ZIKA VIRUS: Experimental therapy.• Several years ago a new effective method of antiviral treatment of

acute and chronic viral diseases was invented in Russia . The medicinal preparation thanks to which hundreds of patients have already completely recovered from viral hepatitis is called «Natrii Hypochloriti». It is widely known in Russia and abroad.

ZIKA VIRUS: Experimental therapy.• A new effective method of antiviral treatment of acute and chronic

viral hepatitis B and C and against other viral diseases was used in medical practice in hospitals. Extensive Research show this method as effective method against severe viral infections, warfare, and outbreak infections, Biological warfare, methicillin-resistant staphylococcus aureus.

ZIKA VIRUS: Experimental therapy.• Sodium hypochlorite as a part of general medical management – I/V

infusion, 300 mg/l. Infusions provided every 24 hours. 10-20 infusions, 400 ml. • However, the dose could be titrated and reduced to 30 mg/l.

ZIKA VIRUS: Experimental therapy.• This method could be effective therapeutically and low cost

treatment.