Drug Discovery Opinion

Topical application of viral entry inhibitors or other microbicides is an attractive strategy to prevent sexual transmission of the human immunodeficiency virus (HIV). Griffithsin, a protein isolated from the red algae Griffithsia sp which grows off the coast of New Zealand, has been shown in vitro to be a potent HIV entry inhibitor, but the cost of production has so far hampered its development.

Writing in the March 30^th Early Edition of PNAS, a multinational team of scientists has now described a breakthrough which should allow the manufacture and isolation of significant amounts of griffithsin as an agricultural crop. Griffithsin was shown to accumulate to a level of more than 1 gram of recombinant protein per kilogram of leaf material of Nicotiana benthamiana when expressed via an infectious tobacco mosaic virus vector. Nicotiana benthamiana, which is native to Australia, is a close relative of the tobacco plant and the authors were able to produce more than 60g of pure griffithsin from a single greenhouse with an area of 5000 square feet. The biophysical characteristics of griffithsin and the nature of the plant host allowed isolation of 99% pure protein after a simple 3-step purification procedure.

The plant-produced protein was found to have broad and potent activity against a panel of primary sexually transmitted HIV-1 isolates representative of viruses prevalent in sub-Saharan Africa, Asia and the West. The recombinant griffithsin was further shown to be non-irritating and non-inflammatory, and to have no mitogenic activity. Since viral entry inhibitors are not commonly used in resource-poor countries, griffithsin produced cost-effectively in Nicotiana benthamiana plants has the potential for prevention and treatment of multi-drug resistant viral infections in developing countries.

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