[GRG] Two nucleoside analogues that work agains Ebola in vivo like RTI’s work on HIV Re: Ebola ethics: in defense of randomization

I’m a fan of antivirals that are nucleoside analoges, like ribavirin, and
old friend of mine. All of the RT inhibitor drugs of HIV work this way, and
are nucleoside drugs.

Ribavirin (alas) works for other hemorrhagic fevers, but not for Ebola.
However, there is a nucleoside analogue called “carbocyclic
3-deazaadenosine.” which DOES work very well. Like ribavirin, it is kinased
up to the phosphate in the body, and then works as that. A few doses result
in survival or most mice with with Ebola, which otherwise have a worse
mortality rate than humans (70%). It was developed by the Army (USAMRID) but
nothing has been heard of it for 13 years, probably because some drug
company didn’t pick it up (where’s the profit?) and it died. But it’s still
there in the litererature, looking like magic. There is also a related
compound called 3-deazaneplanocin A.

One wonders if well-funded joint government/pharma program aimed at making
large batches of these (which they actually did with AZT in 1986) could not
turn out enough to make a difference. It’s harder to scale antibody
production up (this ZMapp stuff), but for chemicals, it’s usually
straightforward. For AZT the limited factor was there wasn’t enough starting
material, since at that time all the thymidine in the world came from salmon
sperm, which wasn’t in unlimited supply. I doubt a similar problem applies
here.

Antiviral Res. 2000 Feb;45(2):135-47.

Treatment of lethal Ebola virus infection in mice with a single dose of an

S-adenosyl-L-homocysteine hydrolase inhibitor.

Bray M(1), Driscoll J, Huggins JW.

Author information:

(1)Department of Viral Therapeutics, United States Army Medical Research
Institute

of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.

bray@ncifcrf.gov

Ebola Zaire virus causes lethal hemorrhagic fever in humans, for which there
is

no effective treatment. A variety of adenosine analogues inhibit the
replication

of Ebola virus in vitro, probably by blocking the cellular enzyme,

S-adenosyl-L-homocysteine hydrolase, thereby indirectly limiting methylation
of

the 5′ cap of viral messenger RNA. We previously observed that adult,

immunocompetent mice treated thrice daily for 9 days with 2.2-20 mg/kg of an

adenosine analogue, carbocyclic 3-deazaadenosine, were protected against
lethal

Ebola virus challenge. We now report that a single inoculation of 80 mg/kg
or

less of the same substance, or of 1 mg/kg or less of another analogue,

3-deazaneplanocin A, provides equal or better protection, without causing
acute

toxicity. One dose of drug given on the first or second day after virus
infection

reduced peak viremia more than 1000-fold, compared with mock-treated
controls,

and resulted in survival of most or all animals. Therapy was less effective
when

administered on the day of challenge, or on the third day postinfection.
Single

or multiple doses of the same medications suppressed Ebola replication in
severe

combined immunodeficient mice, but even daily treatment for 15 consecutive
days

did not eliminate the infection.

PMID: 10809022 [PubMed – indexed for MEDLINE]

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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