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
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.
(1)Department of Viral Therapeutics, United States Army Medical Research
of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
Ebola Zaire virus causes lethal hemorrhagic fever in humans, for which there
no effective treatment. A variety of adenosine analogues inhibit the
of Ebola virus in vitro, probably by blocking the cellular enzyme,
S-adenosyl-L-homocysteine hydrolase, thereby indirectly limiting methylation
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
Ebola virus challenge. We now report that a single inoculation of 80 mg/kg
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
toxicity. One dose of drug given on the first or second day after virus
reduced peak viremia more than 1000-fold, compared with mock-treated
and resulted in survival of most or all animals. Therapy was less effective
administered on the day of challenge, or on the third day postinfection.
or multiple doses of the same medications suppressed Ebola replication in
combined immunodeficient mice, but even daily treatment for 15 consecutive
did not eliminate the infection.
PMID: 10809022 [PubMed – indexed for MEDLINE]