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A folk remedy for killer Ebola

Scientists may have found a cure for the deadly Ebola virus in a plant extract used in traditional African medicine, writes Clare Sansom.

The rare Ebola fever is one of the most dangerous of viral infections for which there is still no effective treatment. But results just presented at the 16th International Botanic Congress in St Louis, Missouri, suggest that a plant widely used in traditional African medicine may contain a compound that is effective against its causative agent, the Ebola virus.

Maurice Iwu, executive director of the Bio-

resources Development and Conservation Programme, based in Maryland, explained that an extract derived from the seeds of Garcinia kola could inhibit this virus in cell culture at non-toxic concentrations.

Garcinia kola is a medium-sized tree that is common in central Africa. Its seeds are used as medicine throughout the region, and extracts are marketed as dietary supplements in the United States. The use of such supplements is regulated by the US Dietary Supplement and Health Education Act, which states that they should be "generally recognised as safe".

Jim Miller, head of applied research at Missouri Botanical Garden, St Louis, says that these regulations are "infinitely easier to pass than the stringent toxicity criteria required by the FDA for the licensing of new drugs".

Iwu and his colleagues identified Garcinia kola as a possible source of drugs using the method called Corbel (clinical observation-based ethnomedical lead). They observe traditional medical practitioners at work in order to identify herbal remedies with effective clinical outcomes. Extracts from promising plants are then tested for activity. Any fraction found to be active is further fractionated and the process repeated until an active compound can be identified. This technique is known as biological assay guided fractionation.

Extracts from Garcinia kola seeds were tested against many complex viral diseases. The active compound, now known to be a biflavonoid, was found to be active against a wide range of viruses including the influenza virus.

In all cases, the active concentration was less than ten times the known minimum toxic concentration. Iwu says: "This gives us a very wide window of opportunity for drug development. We will be able to modify the effective compound with less likelihood of introducing unacceptable toxicity."

The research is focusing on the Ebola virus because of the dangerous nature of the disease it causes. Iwu is conducting pharmacokinetic tests in preparation for animal trials using, initially, a mouse model of Ebola infection.

John Huggins, of the US Army Medical Research Institute of Infective Diseases, who conducted the in vitro tests, emphasised the preliminary nature of the work so far. "This compound has passed the first stage with flying colours, but there is still a long way to go. It may be impossible to develop it into an effective drug."

The main barrier to the further development of this compound may be financial. Pharmaceutical companies are reluctant to invest resources in the development of drugs against extremely rare tropical diseases.

Nor does the answer lie in the public sector. Iwu explains: "This project now falls outside the scope of the NIH (the US National Institutes of Health) programmes, as it has reached the development stage. Normally a candidate drug at this stage would be expected to be taken on by one of the large companies."

Iwu is approaching private charitable foundations. If sufficient funding is secured, and if the in vivo assays are successful, an "investigational drug" might be available for use in epidemics within two years.

Another concern is the affordability of any resulting medicine in very poor areas of central Africa. Alongside the development of the pure compound, Iwu and his colleagues are testing a purified seed extract, known as Kolavirion, that contains the active biflavonoid and some other potentially anti-infective compounds. This

phytomedicine should be much cheaper to develop and produce than a pure drug.

Aspirin and quinine, two of the most widely used of all drugs, are derived from plants that were used as folk remedies. Paclitaxel (taxol) is one of the best known of modern drugs derived from natural products. This drug, extracted from the Pacific yew, has been licensed for treatment of breast, ovarian and lung cancers and Kaposi's sarcoma. So there are precedents for the plan to harness African biodiversity against one of the most dangerous of African diseases.

The Ebola virus

The Ebola and Marburg viruses are the only members of a newly identified family of single-stranded, unsegmented RNA viruses, the filoviridae.

This family is closely related to the rhabdoviridae, which includes the rabies virus, and the paramyxoviridae.

Viruses in this latter family cause childhood diseases such as measles. Filoviruses infect humans and other primates.

Infection with the Ebola virus causes haemorrhagic fevers in humans; death rates in epidemics of the Zaire subtype may be over 80 per cent.

Little is known of the molecular biology of these viruses or the mechanisms by which they cause disease.

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