Cyanovirin

Another contender is a weird, small protein called cyanovirin, which is isolated from a blue-green algae extract. At low concentrations, cyanovirin glues to specific sugars on diverse strains of HIV and doesn't let go, blocking cell fusion-entry of the virus into the host cell and its genes. Since fusion is an early step in HIV's life cycle, this approach is especially promising. Laboratory studies show that cyanovirin is stable, so it won't fall apart, or worse, mutate, and it doesn't harm host cells. "We've tried all the conventional ways to induce the emergence of a cynanovirin-resistant strain [of HIV]," says Dr. Michael Boyd, director of the Laboratory of Drug Discovery, Research and Development at the National Cancer Institute, which isolated the protein. "We haven't been able to do it, nor has any other lab."

Boyd believes cyanovirin could be formulated as a microbicide gel, or genetically engineered into friendly bacteria that normally live in our bodies, and implanted in the vagina. There, the introduced bacterial strain would grow happily, producing cyanovirin at concentrations that would hopefully inactivate HIV and help the body resist common problems like yeast infections caused by Candida.

Functional homologs of cyanovirin-N amenable to mass production in prokaryotic and eukaryotic hosts

Mori,T.; Barrientos,L.G.; Han,Z.Z.; Gronenborn,A.M.; Turpin,J.A.; Boyd,M.R.: Protein Expr.Purif. 26: 42-49, 2002.

Abstract:

Cyanovirin-N (CV-N) is under development as a topical (vaginal or rectal) microbicide to prevent sexual transmission of human immunodeficiency virus (HIV), and an economically feasible means for very large-scale production of the protein is an urgent priority. We observed that N-glycosylation of CV-N in yeast eliminated the anti-HIV activity, and that dimeric forms or aggregates of CV-N occurred under certain conditions, potentially complicating the efficient, large-scale manufacture of pure monomeric CV-N. Therefore, we have expressed and compared CV-N homologs in which the glycosylation-susceptible Asn residue at position 30 was replaced with Ala,Gln or Val, and/or the Pro at position 51 was replaced by Gly to eliminate a potential site of cis-trans isomerization. All of the homologs had anti-HIV activity comparable to wild-type CV-N, and the Pro51Gly homologs exhibited enhanced stability toward denaturants. These glycosylation-resistant,functional cyanovirins are amenable to large-scale production either in bacteria or in eukaryotic hosts such as yeasts or transgenic plants or animals.

Cyanovirin Yogurt

Bharat Ramratnam, an HIV specialist at Brown Medical School, Providence, Rhode Island, and his colleagues have now altered the genetic make-up of L. lactis so that it generates cyanovirin, a drug that has prevented HIV infection in monkeys and human cells, and is on track for human trials in 2007.