AIDS Treatment News #182 - September 3, 1993
John S. James
"Conocurvone" is the name given by scientists at the U.S. National Cancer Institute to a chemical found in the "smoke bush," a plant which grows only in Western Australia. The NCI collected the plant in 1981 for its program of screening for anti-cancer agents, but found that the plant was ineffective for cancer. The remainder of the sample stayed on the shelf, and was later screened for anti-HIV activity. The New Scientist(1) quoted one of the administrators of the screening program as calling conocurvone "extraordinarily exciting." (Conocurvone should not be confused with castanospermine, a different anti-HIV chemical which is found in another Australian plant.)
The first technical information on conocurvone was published July 28, 1993, in the Journal of the American Chemical Society.(2) In laboratory tests, conocurvone was effective in concentrations of 0.02 micromolar in preventing HIV from killing cells. Synthetic and semi-synthetic versions (the latter made from other substances in the plant) worked as well as the natural extract. One chemical relative of conocurvone also appeared to work. It took about 2,500 times the effective anti-HIV concentration to be toxic to the cells in which the virus was being grown. The mechanism of action against HIV is currently unknown, although it is known that the drug does not inhibit either reverse transcriptase or protease, but works in some other way.
An August 31, 1993 article in Bioworld Today, a daily biotechnology newsletter delivered by fax, quoted the researcher who collected the plant as estimating that there are 50 million of them in the Gairdner Mountains of Western Australia.(3) While conocurvone can be synthesized without the plant, only small quantities have been made so far; if there are enough plants, extracting the chemical from them would be the fastest way to make supplies available for development. The article quoted Dr. Michael Boyd of the NCI as noting that "news of this discovery is still very fresh," and that Australian scientists are studying the feasibility of harvesting the wild plants.
A U.S.-Australia dispute over business arrangements for drug development was also described in the New Scientist article.(1) It reported that Australia refused to sign the standard NCI agreement when asked in 1990. Instead, a separate agreement was negotiated. Australia insisted that an agreement must "build in protection for plants in the wild, include Australian scientists in the research and development, and guarantee a 'fair and equitable' share of any commercial benefits from development of the plant." The agreement was reported in SCRIP World Pharmaceutical News.(4) (One side issue raised by this agreement is that if it becomes a precedent, there might be major delays if less- developed countries insist on building their own laboratories and training local scientists before drug-development proceeds. This is not a problem in Western Australia, which already has the world's leading scientific expertise on the smoke bush. The NCI screening program has also discovered potentially important anti-HIV chemicals in three other plants -- in Samoa, Sarawak, and Cameroon. Each of these countries appears to be willing to cooperate with the NCI in the development of these compounds.)
The New Scientist article quoted a representative of the Western Australian government, who was worried about "poaching," as warning that components of the plant could be toxic. (It should also be emphasized that only laboratory anti-HIV activity has been demonstrated, and that no toxicological tests in animals have been conducted yet. Also, it is not certain which of the several species of smoke bush contains significant amounts of conocurvone, or which part of the plant contains the chemical.)
The August 31 Federal Register published a detailed notice from the National Cancer Institute soliciting proposals for development of conocurvone(5); these must be received by November 1. Interested companies can get "a summary of conocurvone's anti-HIV activity, its pharmacological properties, and toxicological information" from the National Cancer Institute; the Federal Register notice tells how to do so. Also, companies can get the NCI patent application if they sign a confidentiality agreement. (The patent will be public after it is issued.)
The U.S. government will grant an exclusive license to a company which shows that it can develop and commercialize the drug. The company will need to negotiate agreements with Australian and Western Australian government agencies concerning collection and use of the plant material, in order to comply "with all applicable Federal and Australian policies related to biodiversity."
References
1. Miller SK and Dayton L. Australia takes tough line on 'HIV plant'. New Scientist. July 3, 1993; page 4.
2. Decosterd LA, Parsons IC, Gustafson KR, and others. Structure, absolute stereochemistry, and synthesis of conocurvone, a potent, novel HIV-inhibitory naphthoquinone trimer from a Conospermum sp. Journal of the American Chemical Society. July 28, 1993; volume 115, pages 6673-6679.
3. Leff DN. NCI offers to license 'intriguing' anti-HIV drug. BioWorld Today. August 31, 1993; volume 4, number 169, page 1.
4. W Australia/NCI 'HIV plant' deal. SCRIP World Pharmaceutical News. July 23, 1993; page 18(1).
5. Opportunity for a license for the preclinical and clinical development of conocurvone as an antiviral agent useful in the treatment of acquired immunodeficiency syndrome (AIDS). Federal Register. August 31, 1993; pages 45902-45903.
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