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Pathway Description
Enfuvirtide Action Pathway
Homo sapiens
Drug Action Pathway
Enfuvirtide is an HIV-1 gp41 fusion inhibitor used in patients experiencing HIV-1 replication who are already being treated with other anti-retrovirals. Enfuvirtide is a biomimetic peptide that was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion.
Enfuvirtide inhibits the envelope glycoprotein by binding to the first heptad-repeat in the gp41 subunut. This disrupts the final stage of fusion with the host cell, thereby preventing the initial attachment of the virus. This significantly decreases viral replication which limits the spread of further infection.
References
Enfuvirtide Pathway References
Greenberg ML, Cammack N: Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother. 2004 Aug;54(2):333-40. doi: 10.1093/jac/dkh330. Epub 2004 Jul 1.
Pubmed: 15231762
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.
Pubmed: 17139284
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.
Pubmed: 17016423
Cabrera C, Marfil S, Garcia E, Martinez-Picado J, Bonjoch A, Bofill M, Moreno S, Ribera E, Domingo P, Clotet B, Ruiz L: Genetic evolution of gp41 reveals a highly exclusive relationship between codons 36, 38 and 43 in gp41 under long-term enfuvirtide-containing salvage regimen. AIDS. 2006 Oct 24;20(16):2075-80. doi: 10.1097/QAD.0b013e3280102377.
Pubmed: 17053353
Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfield-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML: Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol. 2005 Oct;79(19):12447-54. doi: 10.1128/JVI.79.19.12447-12454.2005.
Pubmed: 16160172
Aquaro S, D'Arrigo R, Svicher V, Perri GD, Caputo SL, Visco-Comandini U, Santoro M, Bertoli A, Mazzotta F, Bonora S, Tozzi V, Bellagamba R, Zaccarelli M, Narciso P, Antinori A, Perno CF: Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1-infected patients receiving enfuvirtide treatment. J Antimicrob Chemother. 2006 Oct;58(4):714-22. doi: 10.1093/jac/dkl306. Epub 2006 Aug 5.
Pubmed: 16891628
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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