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Pathway Description
Atazanavir Action Pathway
Homo sapiens
Drug Action Pathway
Atazanavir (formerly known as BMS-232632) is an antiretroviral protease inhibitor used in combination with other antiretrovirals for the treatment of HIV in adults and pediatric patients 3 months of age and older weighing at least 5kg. It is used in combination with cobicistat and other antiretrovirals.
The HIV virus binds and penetrates the host cell. Viral RNA is transcribed into viral DNA via reverse transcriptase. Viral DNA enters the host nucleus and is integrated into the host DNA via integrase. The DNA is then transcribed, creating viral mRNA. Viral mRNA is translater into the gag-pol polyprotein. HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells. HIV-1 protease cleaves the Gag-pol polyprotein into 66 molecular species, including HIV-1 protease, integrase, and reverse transcriptase. Atazanavir selectively inhibits HIV-1 protease. This inhibition prevents the HIV virion from fully maturing and becoming infective. Using the lipid bilayer of the host cell, a virus is formed and released. The inhibition of HIV-1 protease prevents the necessary molecular species from forming, therefore preventing maturation and activation of viral particles. This forms immature, non-infectious viral particles, therefore, Atazanavir prevents the virus from reproducing.
References
Atazanavir Pathway References
Konnyu B, Sadiq SK, Turanyi T, Hirmondo R, Muller B, Krausslich HG, Coveney PV, Muller V: Gag-Pol processing during HIV-1 virion maturation: a systems biology approach. PLoS Comput Biol. 2013;9(6):e1003103. doi: 10.1371/journal.pcbi.1003103. Epub 2013 Jun 6.
Pubmed: 23754941
Zephyr J, Kurt Yilmaz N, Schiffer CA: Viral proteases: Structure, mechanism and inhibition. Enzymes. 2021;50:301-333. doi: 10.1016/bs.enz.2021.09.004. Epub 2021 Nov 17.
Pubmed: 34861941
Louten J. Virus Replication. Essential Human Virology. 2016:49–70. doi: 10.1016/B978-0-12-800947-5.00004-1. Epub 2016 May 6. PMCID: PMC7149683.
Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009.
Pubmed: 19496633
von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. doi: 10.1358/dot.2008.44.2.1137107.
Pubmed: 18389089
Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. doi: 10.2165/00003495-200565160-00010.
Pubmed: 16266202
Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. doi: 10.2165/00003088-200544100-00003.
Pubmed: 16176117
Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir]. Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. doi: 10.1016/S0213-005X(08)76613-8.
Pubmed: 20116610
Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. doi: 10.1592/phco.24.17.1732.52347.
Pubmed: 15585441
Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Dec;81(24):13845-51. doi: 10.1128/JVI.01184-07. Epub 2007 Oct 10.
Pubmed: 17928344
Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. doi: 10.1128/AAC.00149-07. Epub 2007 Jul 16.
Pubmed: 17638694
Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. doi: 10.1586/14787210.6.6.785.
Pubmed: 19053892
Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. doi: 10.2165/00003088-200544100-00003.
Pubmed: 16176117
Pyrko P, Kardosh A, Wang W, Xiong W, Schonthal AH, Chen TC: HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res. 2007 Nov 15;67(22):10920-8. doi: 10.1158/0008-5472.CAN-07-0796.
Pubmed: 18006837
Menendez-Arias L, Tozser J: HIV-1 protease inhibitors: effects on HIV-2 replication and resistance. Trends Pharmacol Sci. 2008 Jan;29(1):42-9. doi: 10.1016/j.tips.2007.10.013. Epub 2007 Dec 4.
Pubmed: 18054799
Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir]. Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. doi: 10.1016/S0213-005X(08)76613-8.
Pubmed: 20116610
Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. doi: 10.1592/phco.24.17.1732.52347.
Pubmed: 15585441
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. doi: 10.1093/nar/30.1.412.
Pubmed: 11752352
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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