Zika virus: experimental treatment.

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
•

• 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

• 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)

• 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

• 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.XS0XOOG
V.dpuf

• 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

• 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:
health-
V.dpuf

• 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:
health-
V.dpuf

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

• Experimental therapy include treatment of viremia with chlorine
containing oxidizers.
• Chlorine? Oxidizers?
• Bleach?
• Not possible?
• Could be harmful?

• 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

• 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.

• 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.

• 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

• 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 .

• 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

• 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.

• 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.

• 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.

• 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.

• 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/

• 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.

• 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.

• 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

• “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

• 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.

• 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.

• 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

• Can we use low dose, nontoxic Sodium hypochlorite (NaOCl) for I/V
therapy of infections diseases?

• 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).

• 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.

• 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.

• 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.

• This method could be effective therapeutically and low cost
treatment.

Zika virus: experimental treatment.

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