Abstract
Viral entry, the first process in the reproduction of viruses, primarily involves attachment of the viral envelope proteins to membranes of the host cell. The crucial components that play an important role in viral entry include viral surface glycoprotein gp120, viral transmembrane glycoprotein gp41, host cell glycoprotein (CD4), and host cell chemokine receptors (CCR5 and CXCR4). Inhibition of the multiple molecular interactions of these components can restrain viruses, such as HIV-1, from fusion with the host cell, blocking them from reproducing. This review article specifically focuses on the recent progress in the development of small-molecule HIV-1 entry inhibitors and incorporates important aspects of their structural modification that lead to the discovery of new molecular scaffolds with more potency.
Keywords: HIV-1 entry inhibitors, Anti-HIV-1, CXCR4 antagonists, CCR5 antagonists, Fusion inhibitors, CD4 mimic molecules.
[http://dx.doi.org/10.1007/978-1-4614-0980-9_10] [PMID: 22297516]
[http://dx.doi.org/10.1038/360358a0] [PMID: 1360148]
[http://dx.doi.org/10.1016/S0092-8674(00)80205-6] [PMID: 9108481]
[http://dx.doi.org/10.1016/S0092-8674(00)81430-0] [PMID: 9630213]
[http://dx.doi.org/10.1371/journal.ppat.0030063] [PMID: 17480119]
[http://dx.doi.org/10.1371/journal.ppat.0020083] [PMID: 16933990]
[http://dx.doi.org/10.1073/pnas.2634931100] [PMID: 14668432]
[http://dx.doi.org/10.1038/nature04817] [PMID: 16728975]
[http://dx.doi.org/10.1371/journal.ppat.1000203] [PMID: 19008954]
[http://dx.doi.org/10.1128/JVI.01764-08] [PMID: 19019953]
[http://dx.doi.org/10.1128/JVI.79.19.12132-12147.2005] [PMID: 16160141]
[http://dx.doi.org/10.1128/JVI.80.9.4388-4395.2006] [PMID: 16611898]
[http://dx.doi.org/10.1128/JVI.74.4.1961-1972.2000] [PMID: 10644369]
[PMID: 2214033]
[http://dx.doi.org/10.1007/s00249-010-0666-z] [PMID: 21258789]
[http://dx.doi.org/10.1002/cmdc.201000289] [PMID: 20845360]
[http://dx.doi.org/10.1016/S0092-8674(00)80205-6] [PMID: 9108481]
[http://dx.doi.org/10.1126/science.6189183] [PMID: 6189183]
[http://dx.doi.org/10.1126/science.6601823] [PMID: 6601823]
[http://dx.doi.org/10.1128/AAC.00942-08] [PMID: 19015347]
[http://dx.doi.org/10.1056/NEJMoa1711460] [PMID: 30110589]
[http://dx.doi.org/10.1080/15284336.2018.1452842] [PMID: 29676212]
[http://dx.doi.org/10.2174/1568026615666150901114527] [PMID: 26324044]
[http://dx.doi.org/10.2174/1872213X11307020006] [PMID: 23578097]
[http://dx.doi.org/10.2174/1389200218666170724112412] [PMID: 28738768]
[http://dx.doi.org/10.2174/1381612811319100003] [PMID: 23092280]
[PMID: 23278399]
[http://dx.doi.org/10.2174/0929867321666131218094559] [PMID: 24350848]
[http://dx.doi.org/10.2174/1570162X14999160224103908] [PMID: 26957202]
[http://dx.doi.org/10.2174/1568026614666140929115202] [PMID: 25262805]
[http://dx.doi.org/10.2174/1381612811319100006] [PMID: 23092284]
[http://dx.doi.org/10.2174/1381612811319100005] [PMID: 23092283]
[http://dx.doi.org/10.2174/1568026614666140827143934] [PMID: 25159164]
[http://dx.doi.org/10.2174/1381612811319100007] [PMID: 23092276]
[http://dx.doi.org/10.1023/A:1021070512287] [PMID: 12465460]
[http://dx.doi.org/10.13005/bpj/1164]
[http://dx.doi.org/10.1016/0092-8674(86)90778-6] [PMID: 2423250]
[PMID: 2355006]
[http://dx.doi.org/10.1038/31405] [PMID: 9641677]
[http://dx.doi.org/10.1016/j.molcel.2010.02.012] [PMID: 20227370]
[http://dx.doi.org/10.1126/science.1145373] [PMID: 17901336]
[http://dx.doi.org/10.1073/pnas.1112391109] [PMID: 22451932]
[http://dx.doi.org/10.1128/JVI.76.19.9888-9899.2002] [PMID: 12208966]
[http://dx.doi.org/10.1128/JVI.02500-06] [PMID: 17360741]
[http://dx.doi.org/10.1016/j.str.2013.05.004] [PMID: 23747109]
[PMID: 10364363]
[http://dx.doi.org/10.1038/nm1196-1174] [PMID: 8898734]
[http://dx.doi.org/10.1186/gb-2006-7-12-243] [PMID: 17201934]
[http://dx.doi.org/10.1146/annurev.iy.12.040194.003113] [PMID: 8011292]
[http://dx.doi.org/10.1146/annurev.immunol.17.1.657] [PMID: 10358771]
[http://dx.doi.org/10.1093/emboj/18.7.1723] [PMID: 10202136]
[http://dx.doi.org/10.1124/pr.54.2.227] [PMID: 12037138]
[PMID: 10699158]
[PMID: 10807766]
[PMID: 16212895]
[http://dx.doi.org/10.1038/382829a0] [PMID: 8752280]
[http://dx.doi.org/10.1038/384288a0]
[http://dx.doi.org/10.1089/dna.1997.16.379] [PMID: 9150425]
[PMID: 10400757]
[http://dx.doi.org/10.1074/jbc.M106582200] [PMID: 11551942]
[http://dx.doi.org/10.3389/fimmu.2015.00429] [PMID: 26347749]
[http://dx.doi.org/10.1126/science.1194396]
[PMID: 10477718]
[http://dx.doi.org/10.1021/bi952950g] [PMID: 8639485]
[http://dx.doi.org/10.1002/1521-4141(200107)31:72170:AID-IMMU21703.0.CO;2-D] [PMID: 11449371]
[http://dx.doi.org/10.1074/jbc.M109198200] [PMID: 11734558]
[http://dx.doi.org/10.1016/j.bbamem.2003.09.006] [PMID: 14637022]
[http://dx.doi.org/10.1074/jbc.M010867200] [PMID: 11116158]
[http://dx.doi.org/10.1111/j.1365-2249.2011.04409.x] [PMID: 21985364]
[http://dx.doi.org/10.1126/science.272.5263.872] [PMID: 8629022]
[http://dx.doi.org/10.1038/381661a0] [PMID: 8649511]
[http://dx.doi.org/10.1038/381667a0] [PMID: 8649512]
[http://dx.doi.org/10.1126/science.272.5270.1955] [PMID: 8658171]
[http://dx.doi.org/10.1126/science.2832945] [PMID: 2832945]
[http://dx.doi.org/10.1016/S0140-6736(89)92628-7] [PMID: 2565516]
[http://dx.doi.org/10.1097/00002030-199207000-00008] [PMID: 1354447]
[http://dx.doi.org/10.1038/382829a0] [PMID: 8752280]
[http://dx.doi.org/10.1038/382833a0] [PMID: 8752281]
[http://dx.doi.org/10.1084/jem.186.1.139] [PMID: 9207008]
[PMID: 9570576]
[http://dx.doi.org/10.2174/1568026615666150901114527] [PMID: 26324044]
[http://dx.doi.org/10.1016/j.bmcl.2009.10.098] [PMID: 19926478]
[http://dx.doi.org/10.1016/j.bmcl.2010.07.106] [PMID: 20728351]
[http://dx.doi.org/10.1016/j.bmc.2011.09.045] [PMID: 22014753]
[http://dx.doi.org/10.1016/j.bmc.2013.02.041] [PMID: 23535561]
[http://dx.doi.org/10.1128/JVI.00540-14] [PMID: 24696475]
[http://dx.doi.org/10.1016/j.virol.2005.06.008] [PMID: 15996703]
[http://dx.doi.org/10.1016/j.bmcl.2015.11.103] [PMID: 26706175]
[http://dx.doi.org/10.1016/j.bmcl.2019.01.011] [PMID: 30665681]
[http://dx.doi.org/10.1016/j.bmc.2011.09.045] [PMID: 22014753]
[http://dx.doi.org/10.1002/cmdc.201500590] [PMID: 26891461]
[http://dx.doi.org/10.1016/j.str.2008.09.005] [PMID: 19000821]
[http://dx.doi.org/10.1016/j.bmc.2010.11.049] [PMID: 21169023]
[http://dx.doi.org/10.1021/bi061193r] [PMID: 16953583]
[http://dx.doi.org/10.1111/j.1747-0285.2010.01075.x] [PMID: 21288305]
[http://dx.doi.org/10.1021/jm300265j] [PMID: 22497421]
[http://dx.doi.org/10.1021/ar4002735] [PMID: 24502450]
[http://dx.doi.org/10.1021/ml300407y] [PMID: 23667716]
[http://dx.doi.org/10.1021/acsmedchemlett.5b00471] [PMID: 26985324]
[http://dx.doi.org/10.1016/j.bmc.2018.10.011] [PMID: 30366786]
[http://dx.doi.org/10.1128/AAC.03339-14] [PMID: 25001301]
[http://dx.doi.org/10.1021/jm3002247] [PMID: 22524483]
[http://dx.doi.org/10.1021/acs.jmedchem.5b00709] [PMID: 26301736]
[http://dx.doi.org/10.1016/j.bmc.2016.09.057] [PMID: 27707628]
[http://dx.doi.org/10.1016/j.ejmech.2018.04.062] [PMID: 29860061]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00179] [PMID: 28266845]
[http://dx.doi.org/10.1021/jm4002988] [PMID: 23710622]
[http://dx.doi.org/10.1016/j.bmc.2015.11.006] [PMID: 26602829]
[PMID: 26491257]
[http://dx.doi.org/10.1107/S0108270197009244] [PMID: 9362555]
[http://dx.doi.org/10.1021/ml500236n] [PMID: 25147619]
[http://dx.doi.org/10.1021/acsmedchemlett.5b00339] [PMID: 26985308]
[http://dx.doi.org/10.1021/acsmedchemlett.7b00376] [PMID: 29152054]
[http://dx.doi.org/10.1016/j.bmc.2013.05.038] [PMID: 23777826]
[http://dx.doi.org/10.1016/j.bmcl.2005.09.069] [PMID: 16246560]
[http://dx.doi.org/10.1016/j.bmc.2007.08.050]
[http://dx.doi.org/10.1007/s00249-010-0666-z] [PMID: 21258789]
[http://dx.doi.org/10.1038/nsmb.1456] [PMID: 18596815]
[http://dx.doi.org/10.1146/annurev.biochem.70.1.777] [PMID: 11395423]
[http://dx.doi.org/10.1016/S0092-8674(00)80205-6] [PMID: 9108481]
[http://dx.doi.org/10.1517/14656566.6.3.453] [PMID: 15794736]
[http://dx.doi.org/10.1592/phco.24.2.198.33141] [PMID: 14998221]
[http://dx.doi.org/10.1021/jm990154t] [PMID: 10464007]
[http://dx.doi.org/10.1021/jm101014v] [PMID: 21190369]
[http://dx.doi.org/10.1021/jm900450n] [PMID: 19746983]
[http://dx.doi.org/10.1016/j.bmcl.2010.01.111] [PMID: 20153190]
[http://dx.doi.org/10.1021/jm200791z] [PMID: 21928824]
[http://dx.doi.org/10.1016/j.bmcl.2009.11.076] [PMID: 20004576]
[http://dx.doi.org/10.1016/j.bmcl.2009.08.018] [PMID: 19699090]
[http://dx.doi.org/10.1016/j.bmcl.2012.02.062] [PMID: 22424973]
[http://dx.doi.org/10.1002/1521-3773(20020118)41:2278:AID-ANIE2783.0.CO;2-A] [PMID: 12491408]
[http://dx.doi.org/10.1016/j.bmcl.2011.12.076] [PMID: 22226654]
[http://dx.doi.org/10.1016/j.bbagen.2005.02.012] [PMID: 15823507]
[http://dx.doi.org/10.1016/j.febslet.2007.05.029] [PMID: 17537437]
[http://dx.doi.org/10.1016/j.bmc.2013.04.046] [PMID: 23673219]
[http://dx.doi.org/10.1007/s00044-014-1185-8]
[http://dx.doi.org/10.1021/jm990154t] [PMID: 10464007]
[http://dx.doi.org/10.1128/AAC.00670-09] [PMID: 19786602]
[http://dx.doi.org/10.1016/j.bbamem.2013.12.022] [PMID: 24388952]
[http://dx.doi.org/10.1021/jm200791z] [PMID: 21928824]
[http://dx.doi.org/10.1021/jm500344y] [PMID: 24856833]
[http://dx.doi.org/10.1016/j.ejmech.2018.10.048] [PMID: 30390441]
[http://dx.doi.org/10.1086/589289] [PMID: 18532888]
[http://dx.doi.org/10.1021/jm800598a] [PMID: 18811134]
[http://dx.doi.org/10.1021/jm200279v] [PMID: 21539377]
[http://dx.doi.org/10.1021/jm100978n] [PMID: 21128663]
[http://dx.doi.org/10.1021/jm800598a] [PMID: 18811134]
[http://dx.doi.org/10.1021/jm200279v] [PMID: 21539377]
[http://dx.doi.org/10.1016/j.bmcl.2011.08.080] [PMID: 21920742]
[http://dx.doi.org/10.1016/j.bmcl.2009.02.014] [PMID: 19233649]
[http://dx.doi.org/10.1016/j.bmcl.2009.07.074] [PMID: 19664920]
[http://dx.doi.org/10.1016/j.bmcl.2011.01.030] [PMID: 21292480]
[http://dx.doi.org/10.1128/AAC.49.8.3474-3482.2005] [PMID: 16048963]
[http://dx.doi.org/10.1128/AAC.49.11.4708-4715.2005] [PMID: 16251315]
[http://dx.doi.org/10.1124/mol.107.042101] [PMID: 18096812]
[http://dx.doi.org/10.1016/j.bmcl.2012.03.019] [PMID: 22464131]
[http://dx.doi.org/10.1039/b707175b] [PMID: 18019544]
[http://dx.doi.org/10.1016/j.bmcl.2004.05.014] [PMID: 15203141]
[http://dx.doi.org/10.1371/journal.pone.0053636] [PMID: 23308267]
[http://dx.doi.org/10.1016/j.ejmech.2013.11.013] [PMID: 24316669]
[http://dx.doi.org/10.1021/ml2002604] [PMID: 24900457]
[http://dx.doi.org/10.1021/jm401101p] [PMID: 24090135]
[http://dx.doi.org/10.1038/s41598-019-41080-w] [PMID: 30886166]
[http://dx.doi.org/10.1126/science.1241475] [PMID: 24030490]
[http://dx.doi.org/10.1021/jm100073m] [PMID: 20297846]
[http://dx.doi.org/10.1002/ddr.20469]
[http://dx.doi.org/10.1128/AAC.00013-07] [PMID: 17452489]
[http://dx.doi.org/10.1128/AAC.01293-09] [PMID: 19949058]
[http://dx.doi.org/10.1021/jm801065q] [PMID: 19053768]
[http://dx.doi.org/10.1016/j.bmcl.2013.01.107] [PMID: 23434419]
[http://dx.doi.org/10.1021/ml400183q] [PMID: 24936240]
[http://dx.doi.org/10.1124/mol.108.049775] [PMID: 18768385]
[http://dx.doi.org/10.1021/acsmedchemlett.7b00406] [PMID: 29456793]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00450] [PMID: 30052039]
[http://dx.doi.org/10.1021/acsmedchemlett.7b00381] [PMID: 29348805]
[http://dx.doi.org/10.1016/j.bmcl.2011.01.021] [PMID: 21295470]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01420] [PMID: 29350534]
[http://dx.doi.org/10.1021/acsmedchemlett.8b00030] [PMID: 29795757]
[http://dx.doi.org/10.1002/cmdc.201100525] [PMID: 22190478]
[http://dx.doi.org/10.1021/jm501772w] [PMID: 25584630]
[http://dx.doi.org/10.7150/thno.5376] [PMID: 23382786]
[http://dx.doi.org/10.1016/j.bmcl.2009.09.056] [PMID: 19818609]
[http://dx.doi.org/10.1016/j.ejmech.2018.02.042] [PMID: 29494843]