118371PathwayIndinavir Action PathwayIndinavir is a protease inhibitor used to treat HIV infection.
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. Indinavir competitively binds to the active site of 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, Indinavir prevents the virus from reproducing.Drug ActionPW127500CenterPathwayVisualizationContext12777631003400#000099PathwayVisualization118206118371Indinavir PathwayIndinavir is a protease inhibitor used to treat HIV infection.
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. Indinavir competitively binds to the active site of 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, Indinavir prevents the virus from reproducing.Drug134009023754941Konnyu 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 6.118371Pathway34009134861941Zephyr 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 17.118371Pathway340092Louten J. Virus Replication. Essential Human Virology. 2016:49–70. doi: 10.1016/B978-0-12-800947-5.00004-1. Epub 2016 May 6. PMCID: PMC7149683.118371Pathway34009317849388Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. doi: 10.1002/jcc.20821.118371Pathway34009417638694Dandache 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 16.118371Pathway3400959297727Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, Beijnen JH: Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997 Aug;19(4):159-75. doi: 10.1023/a:1008629608556.118371Pathway3400968724039Stein DS, Fish DG, Bilello JA, Preston SL, Martineau GL, Drusano GL: A 24-week open-label phase I/II evaluation of the HIV protease inhibitor MK-639 (indinavir). AIDS. 1996 May;10(5):485-92. doi: 10.1097/00002030-199605000-00006.118371Pathway34009729126136118371Pathway1CellCL:00000002Platelet CL:00002335HepatocyteCL:00001823NeuronCL:00005404CardiomyocyteCL:000074623T CellCL:000008418ErythrocyteCL:000023228MacrophageCL:00002351Homo sapiens9606EukaryoteHuman3Escherichia coli562Prokaryote12Mus musculus10090EukaryoteMouse24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog6Caenorhabditis elegans6239EukaryoteRoundworm49Bathymodiolus platifrons220390EukaryoteDeep sea mussel60Nitzschia sp.0001EukaryoteNitzschia42Bacteria2ProkaryoteBacteria17Rattus norvegicus10116EukaryoteRat5Bos taurus9913EukaryoteCattle10Drosophila melanogaster7227EukaryoteFruit fly186Human immunodeficiency virus type 111676EukaryoteHIV-15CytoplasmGO:00057373Mitochondrial MatrixGO:00057591CytosolGO:00058294PeroxisomeGO:000577713Endoplasmic ReticulumGO:000578314Mitochondrial Outer MembraneGO:00057412MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578925Golgi ApparatusGO:000579410Cell MembraneGO:000588627Peroxisome MembraneGO:000577815NucleusGO:000563426Golgi Apparatus MembraneGO:000013935ChloroplastGO:000950711Extracellular SpaceGO:000561512Mitochondrial Inner MembraneGO:00057432Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:00014845cardiocyteBTO:00015398Blood VesselBTO:000110274118511PW_BS0000084311PW_BS00000416212PW_BS0000162111PW_BS000002261115PW_BS0000265411PW_BS000005181311PW_BS000018221411PW_BS000022397113PW_BS0000393211PW_BS000003215114PW_BS00002146114PW_BS00004649711PW_BS000049432511PW_BS00004314101PW_BS000014101711PW_BS000010592711PW_BS000059231511PW_BS00002329111PW_BS000029711PW_BS000007311511PW_BS000031918511PW_BS000091541315PW_BS000054562611PW_BS0000561041431PW_BS0001041115121PW_BS0001111122121PW_BS000112103331PW_BS0001031471241PW_BS000147151141PW_BS0001511553241PW_BS0001551613181PW_BS00016116611PW_BS0001661783211PW_BS0001781644PW_BS0001641601181PW_BS00016019914181PW_BS000024205561PW_BS000024206261PW_BS0000242137181PW_BS0000242111018PW_BS00002421425181PW_BS0000242164181PW_BS0000241985181PW_BS000024222341PW_BS0000241321121PW_BS00013221013181PW_BS0000242253541PW_BS0000242491341PW_BS0000242881441PW_BS000024226441PW_BS0000242905491PW_BS0000242851041PW_BS0000243081011PW_BS0000241333121PW_BS00013332914121PW_BS0000283361121PW_BS0000283344121PW_BS00002833527121PW_BS0000281151012PW_BS0001153317121PW_BS00002835625121PW_BS00002813013121PW_BS0001303683601PW_BS000028184121PW_BS000024372102PW_BS0000281181171PW_BS0001181355171PW_BS00013515111PW_BS000015253541PW_BS0000245181PW_BS000051383751PW_BS00010027151PW_BS0000272231241PW_BS000024390761PW_BS0001123987171PW_BS000113406351PW_BS000115122551PW_BS0001223821451PW_BS000100407251PW_BS000115408451PW_BS000115124151PW_BS000124429151PW_BS0001154192551PW_BS0001151251351PW_BS000125405105PW_BS0001154222751PW_BS0001151203171PW_BS00012039914171PW_BS0001131192171PW_BS0001193744171PW_BS0000534641171PW_BS00011545525171PW_BS00011513613171PW_BS0001363761017PW_BS00005337527171PW_BS0000532975101PW_BS00002448414101PW_BS0001154793101PW_BS0001154812101PW_BS0001154824101PW_BS0001152991101PW_BS0000244957101PW_BS00011549025101PW_BS0001154781010PW_BS00011549127101PW_BS00011530013101PW_BS0000243891461PW_BS000112501361PW_BS000115502461PW_BS000115388161PW_BS0001125072561PW_BS000115209106PW_BS0000245082761PW_BS0001153951361PW_BS0001138911421PW_BS000552825151861PW_BS00054882311861PW_BS000548116481123PW_BS0005831317815123PW_BS000588134081518623PW_BS00058913418118623PW_BS00058910761118PW_BS000578116985128PW_BS000583824101861PW_BS00054813041861PW_BS0005881000810123PW_BS000574131681018623PW_BS000588423MagnesiumHMDB0000547Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.22537-22-0C003058881842013-HYDROXY-MAGNESIUM-PROTOPORP865DB01378[Mg++]MgInChI=1S/Mg/q+2JLVVSXFLKOJNIY-UHFFFAOYSA-Nmagnesium(2+) ion24.30523.9850418980magnesium(2+) ion22FDB003518Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+PW_C000423Mg2+868227426816476272726811581918883229363998339922111674614834915294317641421241024115929422331262933737454031477491486954497456525310453291115356112537610359061475934151603815560941616250166648417865941646881160697919971702057194206722721372332117250214731021673131987473222117631321184321012312225123242491251328812581226127292901527528515337308771371337723632977937336783933347841733578489115785223317853635678574130800203688004518480048372806231188065413580865158096525381841519383238394900271085962231105593901156873981199744061200701221202473821207024071209814081211811241212654291213194191219241251220864051224084221227591201229213991233071191235463741238354641238894551244771361246373761249783751254472971255984841256694791257774811259214821259472991259734951260004901262434781265534911267533001271253891271645011273805021274073881274515071278042091281255081283473951407738918766IndinavirHMDB0014369Indinavir is only found in individuals that have used or taken this drug. It is a potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [PubChem]Indinavir inhibits the HIV viral protease enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.150378-17-9C070515362440440324515036DB00224CC(C)(C)NC(=O)[C@@H]1CN(CC2=CN=CC=C2)CCN1C[C@@H](O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]1[C@H](O)CC2=CC=CC=C12C36H47N5O4InChI=1S/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1CBVCZFGXHXORBI-PXQQMZJSSA-N(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-4-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl}butyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide613.7895613.362805017-4.114indinavir01Indinavir sulfate;Compound j;Indinavir sulphate;(1(1s,2r),5(s))-2,3,5-trideoxy-n-(2,3-dihydro-2-hydroxy-1h-inden-1-yl)-5-(2-(((1,1-dimethylethyl)amino)carbonyl)-4-(3-pyridinylmethyl)-1-piperazinyl)-2-(phenylmethyl)-d-erythro-pentonamidePW_C008766Indinav390HIV-1 DNADNAAF033819.3PW_NA000390HIV-1 DNA1447082314471221447158251447198231447811164144783131714493813401449421341352DNADNAPW_NA000352140032823142328214300110761447092314471682514478413171449391340388Single strand RNARNAPW_NA000388ssRNA143857116914471121447188231447801164144941134124259IntegraseQ7ZJM1pol1861447102314471782514473321447353081447408241447451304144749714478213171449401340144950100024257Reverse transcriptase/RNaseHQ72547pol18614469421447078231447791164144943134124261Gag-Pol polyproteinQ9QBZ5
Gag-Pol polyprotein
Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
gag-pol3023.4.23.16; 2.7.7.49; 2.7.7.7; 3.1.26.13; 3.1.13.2; 2.7.7.-; 3.1.-.-14473430814473982414478511641447861000144944131624262HIV-1 proteaseO90777HIV-1 protease30314473630814474182414474613041447507144752511447871000144945131623596Reverse transcriptase proteinQ9WJQ2reverse transcriptase1861399422313994321400318231447373081447428241447471304144751716184Integrase186PW_P016184264572425916164Reverse transcriptase/RNaseH186PW_P016164264362425716193Gag-Pol polyprotein186PW_P0161932646824261121721423316194HIV-1 protease186PW_P0161942646924262214533Reverse Transcriptase186PW_P0145332451423596219241falsePW_R219241Right8455403901NucleicAcidfalse8455413521NucleicAcidfalse20870716184219242falsePW_R219242Right8455423881NucleicAcidfalse8455433901NucleicAcidfalse20870816164219248falsePW_R219248Right845554161931ProteinComplexfalse845555161841ProteinComplexfalse845556161941ProteinComplexfalse845557145331ProteinComplexfalse2087141619414836PW_T014836Diffusion152853901NucleicAcid223Right4321InhibitionPW_I00432186418766Compound1864216194ProteinComplex131932014233089false948211720regular1002531932038766308158false198177910regular30028051633901223false2202137114150nucleic_acidregular1507051643521223false2792137114150regular150705165388962false120640114120nucleic_acidregular1201155166390122false220639614150nucleic_acidregular15070123542624259232false250213718subunitregular1507012354272425722false16713968subunitregular15070123542824261308136false91121178subunitregular1751551235429242591304167false67615128subunitregular1408512354302426213042false92115028subunitregular150701235431235961304113false71116378subunitregular1608012354322426230899false92318848subunitregular150709726001618411820623122897712354269726011616411820621228978123542797260216193118206308122897912354285248031932014374214Cofactor97260316184118206130412289801235429972604161941182061304122898112354309726051453311820613041228982123543197260616194118206308122898312354324374210M2352 1406 C2429 1406 2436 1406 2502 1406 5false184374211M2792 1406 C2746 1406 2706 1406 2652 1406 5false18trueM 667.9468550441649 1124.261556296296 L 653 1123 L 659.3808877211858 1136.5751343230784false4374212M1321 431 C1391 432 1611 431 1671 431 5false184374213M2206 431 C2148 435 1877 430 1821 431 5false18trueM 796.9468550441649 279.261556296296 L 782 278 L 788.3808877211858 291.5751343230783false4374214M568.5 2032 L568.5 2082 L618.5 2032 z10true184374215M1001 2124 C1001 2080 998 2014 998 1954 5false18falsefalse4374216M816 1552 C966 1550 998 1797 998 1884 5false18trueM 46.946855044164835 2494.261556296296 L 32 2493 L 38.38088772118584 2506.575134323078false4374217M996 1572 C995 1634 996 1806 998 1884 5false18trueM 46.946855044164835 2494.261556296296 L 32 2493 L 38.38088772118584 2506.575134323078false4374218M871 1677 C957 1674 998 1814 998 1884 5false18trueM 46.946855044164835 2494.261556296296 L 32 2493 L 38.38088772118584 2506.575134323078false4374223M2867 1441 C2866 1480 2869 1656 2870 1699 218false18trueM 1149.58403510137 1816.5831231661625 L 1162 1825 L 1163.081246709313 1810.0390205683718false4374224M2397 2125 C2396 2162 2397 2210 2397 2285 218false18trueM 1093.5 2493.0096189432334 L 1101 2506 L 1108.5 2493.0096189432334false4374225M1950 2388.666748046875 C2021 2388.666748046875 2241 2389.666748046875 2300 2389.666748046875 83false18trueM 734.9903810567666 2553.166748046875 L 722 2560.666748046875 L 734.9903810567666 2568.166748046875false4374226M1296 2197.666748046875 C1223 2196.666748046875 1146 2198 1086 2197 149false17trueM 1112.0096189432334 2905.5 L 1125 2898 L 1112.0096189432334 2890.5false4374227M1857 2518.666748046875 C1856 2542.666748046875 1859 2689.666748046875 1859 2727.666748046875 218false18trueM 644.844329429519 2763.4835625939295 L 652 2776.666748046875 L 659.8391382198117 2763.878162825253false4374228M2281 466 C2281 496 2277 1341 2277 1371 83true184374229M2277 1371 C2277 1341 2281 496 2281 466 83false18trueM 1090.9468550441647 243.26155629629605 L 1076 242 L 1082.380887721186 255.57513432307834false4374230M498 1919 C528 1919 893 1919 923 1919 148true184374231M923 1919 C893 1919 544 1918 498 1919 148false18falsetrueM 19.565967322978995 1668.6864219732176 L 11 1681 L 2.4340326770210066 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222 C929 172 979 122 1029 122 C1680 122 2525 122 3176 122 C3226 122 3276 172 3276 222 C3276 1025 3276 2070 3276 2873 C3276 2923 3226 2973 3176 2973 C2525 2973 1680 2973 1029 2973 C979 2973 929 2923 929 2873 C929 2070 929 1025 929 222 1true62347.02851.0476519M2081 1130 C2081 1080 2131 1030 2181 1030 C2436 1030 2769 1030 3024 1030 C3074 1030 3124 1080 3124 1130 C3124 1577 3124 2159 3124 2606 C3124 2656 3074 2706 3024 2706 C2769 2706 2436 2706 2181 2706 C2131 2706 2081 2656 2081 2606 C2081 2159 2081 1577 2081 1130 93true61043.01676.0893824235HIV Infected Cell126033202.22.220015893825235Integration24151414191.61.620015893826235Nucleus2375952201.91.920015893827235Viral RNA1105529201.61.620015893828235Viral DNA2115545201.61.62001589382915Viral DNA is integrated into the host DNA23201045203.13.116015893830235Transcription23801836201.61.620015893831235Translation14652743201.91.92001589383215Viral mRNA is translated into the gag-pol polyprotein which binds to the lipid bilayer of the host cell.13792007202.82.816015893833235Viral mRNA16862470201.61.620015893834235Viral mRNA22812505201.61.620015893835235Cytosol2595223202.22.22001589383615Indinavir inhibits HIV-1 protease. This inhiibition prevents the HIV virion from fully maturing and becoming infective.2602027203.43.41601589383715Using the lipid bilayer of the host cell, a virus is formed and released. The inhibition of HIV-1 protease prevents the maturation and release of the new viral cell.590780202.82.81601589383815Viral DNA is transcribed into viral mRNA25852285202.82.81601589383915HIV-1 protease cleaves the Gag-pol polyprotein into 66 molecular species, including HIV-1 protease, integrase, and reverse transcriptase.11001752203.13.11601589384015HIV virus attaches and penetrates host cell.145140202.82.81601528307016541437209910503111269239#FFF9C9410121642