The Protein Cyanovirin Inactivates HIV and Influenza
Posted Jun 15 2010 5:00pm
Description of Invention: Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms. CV-N also blocks cell-to-cell transmission of HIV infection. CV-N interacts in an unusual manner with the viral envelope, binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, CV-N and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans.
The described technology includes glycosylation-resistant mutants, which code sequences to enable ultra large-scale recombinant production of functional CV-Ns in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention.
CV-N was benign in vivo when tested in the rabbit/monkey vaginal toxicity/irritancy model and was not cytotoxic in vitro against human immune cells and lactobacilli. CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation and is amenable to very large-scale production by a variety of genetic engineering approaches.
Therapeutics and prevention of HIV and influenza infections
Topical microbicide to protect HIV infection
Ex vivo devices incorporating CV-N to remove or inactivate HIV from fluid samples
Potent anti-HIV and anti-influenza activity
Can be applied both systematically or locally
Can be applied both in vivo and ex vivo
Inexpensive and large scale manufacturing
Preclinical (rabbit/monkey) data in microbicide field are available at this time.
Initial animal efficacy studies (both mouse and ferret) against influenza (H1N1) have been completed and published.
Inventors: Michael R Boyd (NCI) Kirk R Gustafson (NCI) Robert H Shoemaker (NCI) James B McMahon (NCI) Barry R O'Keefe (NCI)
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B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-1356. [ PubMed abs ]
CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses. 2004 Jan; 20(1):11-18. [ PubMed abs ]
DF Smee, KW Bailey, MH Wong, BR O'Keefe, KR Gustafson, VP Mishin, LV Gubareva. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res. 2008 Dec;80(3):266-271. [ PubMed abs ]
Licensing Status: Available for licensing.
Collaborative Research Opportunity: The National Cancer Institute, Molecular Targets Laboratory , is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or email@example.com for more information.
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