Science in Society Archive

Ebola Virus Emerging Therapies

World mobilized to control largest outbreak of virus causing deadly haemorrhagic fever. Prof Joe Cummins

Largest outbreak in history and mutating rapidly

The Ebola virus epidemic is spreading rapidly in Africa but has not yet impacted the populations of other continents. The virus was first detected in humans during the 1970s when the spread of the disease to humans was from contact with wild animals particularly bats. However, during the following years the virus spread to human populations and current genetic evidence indicates that the virus is now mainly transmitted from humans to humans and that the virulent virus is mutating rapidly. A genetic analysis in its largest outbreak shows that Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria.  Sequencing has been done on 99 Ebola virus genomes from 78 patients in Sierra Leone [1]. There was rapid accumulation of interhost and intrahost genetic variation, allowing the characterization of viral transmission over the initial weeks of the epidemic.

Transmission pattern defined

This West African variant likely diverged from Middle African lineages about 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Since many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak  response. The best evidence is that the virus mutates extensively and spreads mainly now by human to human contact. In the absence of effective therapies the virus poses a global threat.

Potential therapies

Previously I described the  production of ZMapp monoclonal  antibody in tobacco plants and the early success in treating Ebola infection [2].  On 4-5 September, the World Health Organization (WHO), 150 Ebola scientists, industry executives, clinical-trials experts, ethicists and regulatory officials met at the WHO’s headquarters in Geneva, Switzerland, to identify and prioritize the most promising products for use in clinical trials. Four drugs and two vaccines lead among the candidates for treatment of Ebola victims. The ZMapp monoclonal antibody cocktail leads the list of drugs with evidence that monkeys are protected by treatment with the drug and seven humans  infected with the virus five of whom survived and two died. The drug is currently in phase one clinical trial with healthy volunteers [3].

Tekmira pharmaceuticals of Canada has undertaken clinical trials of a small RNA inhibitor (RNAi) which prevents replication of the Ebola virus [4]. US FDA (Food and Drug administration) expressed concern over a potential cytokine release induced by the drug. Flavipiravir a small molecule inhibitor the viral RNA polymerase  has been effective in treating mice infected by Ebola virus and has proceeded to phase 3 clinical trials with humans infected with influenza virus [5]. Another small molecule inhibitor of virus RNA polymerase, designated BCX4430, protects monkeys infected with Marburg virus, a filovirus related to Ebola [6].

The vaccine candidate NIAID/GSK from the US National Institute of Allergy and Infectious Diseases includes a chimpanzee adenovirus carrying segments of Ebola virus genetic material, and was found safe for humans in preclinical trials [7]. The vaccine VSV-EBOV produced by NewLink Genetics USA is Vesicular Stomatitis Virus–Based Ebola Vaccine containing segments of Ebola virus genetic material. It prevents lethal Ebola infection in non-human primates [8].

The conclusion of the two day meeting was to postpone decision on the use of vaccines, monoclonal antibodies, and small RNA until November 2014 [9]. The only therapies immediately approved were blood sera and whole blood transfusions from patients who survive Ebola infection.

Tobacco therapeutics

The antibodies are produced in a Australian strain of the tobacco plant (Nicotiana benthamiana) by Kentucky Bioprocessing in Owensboro, Kentucky, a 23-acre, contract R&D and protein production company that was acquired in January by Reynolds America, Inc, the parent company of R.J. Reynolds Tobacco. In 2007, Mapp engaged KBP to manufacture a post-exposure treatment for Ebola infection. A number of therapeutic monoclonal antibodies are being produced in the Kentucky plant. According to KPB the tobacco plants are produced in an open field then transferred to a greenhouse where the leaves of the tobacco plants are treated using magnifection, then harvested and processed under stringent conditions.  RJ Reynolds is the second largest producer of cigarettes in the United States and monoclonal antibodies have been developed successfully elsewhere to treat small cell lung cancer [10]. It is hoped that that the corporation will be able to participate in the treatment of lung cancer at modest cost to the patients.

To conclude

WHO is faced with a dire need to prevent the Ebola epidemic spiralling out of control, and the world is crying for out for prompt and effective action to ease the suffering of those infected with Ebola virus.

Article first published 08/09/14


References

  1. Gire S etal Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak scienceXpress Published online 28 August 2014 [DOI:10.1126/science.1254837]
  2. Cummins J. Virus Vaccine Made In Tobacco Plants to Control Ebola I-SIS Report 26/08/14 http://www.i- is.org.uk/
  3. Butler D. Ebola drug trials set to begin amid crisis Nature 513,13–14 (04 September 2014) doi:10.1038/513013a
  4. Tekmira. FDA Modifies Tekmira's TKM-Ebola Clinical Hold to Partial Hold Enabling Use of Tekmira's Investigational Therapeutic in Ebola-Infected Patients August 7, 2014 http://investor.tekmirapharm.com/releasedetail.cfm?ReleaseID=865208
  5. Favipiravir. Wikipedia 2014 http://en.wikipedia.org/wiki/Favipiravir
  6. Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S.Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430.Nature. 2014 Apr 17;508(7496):402-5. doi: 10.1038/nature13027.
  7. National Institute of Allergy and Infectious Disease QUESTIONS AND ANSWERS Phase 1 Clinical Trials of NIAID/GSK Investigational Ebola August 28, 2014 http://www.niaid.nih.gov/news/QA/Pages/EbolaVaxQA.aspx
  8. Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H.Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy.J Infect Dis. 2011 Nov;204 Suppl 3:S1066-74. doi: 10.1093/infdis/jir348.
  9. World Health Organization Consultation on potential Ebola therapies and vaccines Geneva, Swizerland - 4-5 September 2014 http://www.who.int/medicines/en/
  10. Rolfo C, Sortino G, Smits E, Passiglia F, Bronte G, Castiglia M, Russo A, Santos ES, Janssens A, Pauwels P, Raez L.Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer? Expert Rev Anticancer Ther 2014 Aug 22:1-15. [Epub ahead of print]
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    Stephen Porter Comment left 9th September 2014 03:03:20
    These might be worth a look: Ebola virus and vitamin C (starting at 180 grams intravenous sodium ascorbate per 24 hours and increasing as necessary to break fever). http://vitamincfoundation.org/www.orthomed.com/ebola.htm http://www.doctoryourself.com/levy.html http://www.breathing.com/articles/vitamin-c.htm Do an Internet search for your home town and intravenous vitamin C so you know where to go if this becomes necessary. Naturopathic doctors provide this service. However, if the government declares martial law (http://drsircus.com/medicine/ebola-catastrophic-pandemic) and locks up everyone showing symptoms (or even without symptoms if they may have been exposed to the virus), then you will lose control of your treatment. So you will have a better chance of retaining control of your health if you (and the people around you) take measures now to prevent the disease. Ebola - Saving Lives with Natural Allopathic Medicine - selenium, vitamin E, magnesium, vitamin C, sodium bicarbonate, vitamin D, iodine, hyperthermia, and glutathione. http://drsircus.com/medicine/ebola-saving-lives-natural-allopathic-medicine http://drsircus.com/medicine/glutathione-selenium-viral-infections http://drsircus.com/books/e-book/treating-ebola-ebook/ Ebola and dehydration. http://drsircus.com/medicine/ebola-dehydration-re-mineralization-rehydration-can-save-lives Ebola and selenium deficiency. http://www.drpasswater.com/nutrition_library/selenium_aids.html http://www.holistic-online.com/Remedies/Biot/biot_anthrax-selenium-6-nat-rem.htm http://www.whale.to/m/selenium.html http://orthomolecular.org/library/jom/1995/articles/1995-v10n0304-p131.shtml http://jid.oxfordjournals.org/content/182/Supplement_1/S93.full Vital infections are pH sensitive. http://drsircus.com/medicine/viral-spread-ph-sensitive Strengthen the immune system. http://drsircus.com/medicine/immune-system-cures-ebola-fifth-percent-of-the-time

    Stephen Porter Comment left 9th September 2014 17:05:54
    "The microbe is nothing. The terrain is everything." - Claude Bernard (1813-1878) How do we create a terrain that will resist infection? According to Claude Bernard, healthy terrain involves four factors: 1. alkalinity 2. negative electrical charge 3. nutrition 4. toxins See http://www.whale.to/a/lost_history_of_medicine.html Attaining an alkaline terrain is discussed in detail here http://www.alkalizeforhealth.net/salivaphtest.htm "If our internal environment was changed from an acidic oxygen deprived environment to an alkaline environment full of oxygen, viruses, bacteria and fungus cannot live." - Dr. Otto Warburg Negative electrical charge begins with grounding the human body to the earth (www.earthing.com) because the surface of the earth has a negative electrical charge. The negative charge is stored in the body as liquid crystal water, which acts as a battery to constantly recharge the body's antioxidant system. Glutathione is the main antioxidant inside cells. Vitamin C is the main antioxidant outside cells. Vitamin E is the main fat soluble antioxidant and prevents oxidation of lipids. Vitamin A is the main antioxidant for the skin, which includes the lining of the lungs, esophagus, stomach and intestines. Alpha Lipoic Acid (ALA) is the main antioxidant for mitochondria. ALA is soluble in both water and fat and easily penetrates the blood-brain barrier. Nutrition to prevent infection will include the following: Vitamin C is antiviral, antitoxin and antihistamine; Vitamin D is antiviral and antibacterial; Iodine is antiviral, antibacterial and antifungal; Glutathione is antiviral, antibacterial, antifungal and antiparasite. The four components of glutathione are selenium, plus the amino acids cysteine, glutamine, and tryptophan. Since tryptophan is denatured by heat, a significant portion of the diet should be raw foods. There are many ways to minimize toxins in the body. These would include a clean diet, adequate sleep, daily exercise, non-smoking, sweating, maintaining a healthy colon, dealing effectively with stress, and much more. To prove his point, Claude Bernard reportedly drank a glass of cholera tainted water. Cholera was the Ebola of his day.

    Todd millions Comment left 11th September 2014 16:04:49
    '-sera and whole blood transfusions from surviours'. Can this be 'amplified'in horses?As per 'classic'Diptheria serums from 1890's?How hard would this be to do in the 'feild'?As in local vet facilities and medical schools?My(MD) grandfather noticed the old smart money was moving from tabacco to parmacuticails in the 1950's-This renolds'synergey'is somewhat alarming to me.Public vaccinations were only possible with public vaccine production right from the get go(NewYork,pre WW1)-all private production was too tainted and of variable effectiveness.Now the public labs are privatized,we have the same 'limits'reoccuring and our health depatments are staffed by whores and bagmen with a icing of useful idiots.

    Sandy Wilson Comment left 13th October 2014 05:05:45
    Instead of therapies and questionable government actions regarding vaccines - I don't trust any government not to start putting "other" things in vaccines, considering the UN Agenda 21 policy on depopulation, isn't it more appropriate to follow what these people have done? http://www.npr.org/blogs/goatsandsoda/2014/10/06/354054915/firestone-did-what-governments-have-not-stopped-ebola-in-its-tracks?utm_source=npr_newsletter&utm_medium=email&utm_content=20141012&utm_campaign=mostemailed&utm_term=nprnews

    Christine T. Comment left 22nd October 2014 16:04:32
    Maybe it is worth to go back to some natural remedies in the fight against Ebola? Older studies done by Orthomolecular Group of Scientists at: http://www.orthomolecular.org/ point to an interesting paper: http://orthomolecular.org/library/jom/1995/pdf/1995-v10n0304-p131.pdf The source for the mentioned natural solution to viral infections can be found at: http://www.anh-usa.org/ebola-can-be-prevented-and-treated-naturally/