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Enfuvirtide is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and children 6 years of age and older. Enfuvirtide is for people who have not responded well enough to treatment with other anti-HIV medicines. Enfuvirtide is always used in combination with other anti-HIV medicines. Enfuvirtide is a type of anti-HIV medicine called a fusion inhibitor. Fusion inhibitors work by blocking HIV’s ability to merge with and infect healthy cells. When used with other anti-HIV medicines, enfuvirtide may lower the amount of HIV in the blood. Enfuvirtide does not cure HIV/AIDS. It is not known if enfuvirtide reduces the risk of passing HIV to other people.
Mechanism of Action: Enfuvirtide binds to a region of the gp41 subunit of the HIV-1 envelope glycoprotein (first heptad repeat domain – HR1), that mediates a conformational change required for viral and host-cell membrane fusion. This conformational change is essential to bring the viral and cellular membranes into close enough proximity for fusion and subsequent viral entry into the host-cell. Enfuvirtide prevents this step and thus also the infection of the cell by HIV-1.
Since the first appearance of enfuvirtide, the search for peptide drugs against HIV has been a growing field of research and several candidates proved to be efficient in vitro. As our knowledge of HIV structure and function progresses, more sophisticated peptide designs are developed in order to overcome viral resistance to previous drugs. The initial view of the mechanism of action of these peptides, that is, binding to NHR region and block 6-helix bundle formation, has been refined over the years. Other factors besides gp41-peptide binding can contribute to explain the mode of action of these peptides. In fact enfuvirtide does not form stable 6-helix bundle structures with N36, a NHR derived peptide, contrary to C34, another CHR derived peptide. Moreover, peptides derived from the membrane-spanning domain in gp41 and the co-receptor binding site in gp120 inhibited enfuvirtide antiviral activity, meaning that other sites in the viral envelope could be targeted by enfuvirtide.