Structural studies of the HIV-1 integrase protein: Compound screening and characterization of a DNA-binding inhibitor

PLoS ONE

Volumn 10, Issue 6, 2015, Pages

  Quashie, Peter K ^a,b   Han, Ying Shan ^a   Hassounah, Said ^a,b   Mesplède, Thibault ^a   Wainberg, Mark A ^a,b,c  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FZ 41; HDS 1; INTEGRASE; INTEGRASE INHIBITOR; LENS EPITHELIUM DERIVED GROWTH FACTOR; RALTEGRAVIR; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG; ZIDOVUDINE; ZINC 00337691; ZINC 01689544; ZINC 01703953; ZINC 05004388; MOLECULAR LIBRARY; P31 INTEGRASE PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1; VIRUS RNA;

ALLOSTERISM; ARTICLE; BINDING SITE; COMPUTER PROGRAM; CONTROLLED STUDY; DNA BINDING; DRUG SCREENING; DRUG STRUCTURE; ENZYME INHIBITION; ENZYME STRUCTURE; MOLECULAR DOCKING; PROTEIN DNA BINDING; SPUMAVIRUS; STATISTICAL MODEL; STRUCTURAL HOMOLOGY; STRUCTURE ANALYSIS; CELL LINE; CHEMICAL DATABASE; CHEMISTRY; DIMERIZATION; DRUG EFFECTS; ENZYMOLOGY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; METABOLISM; MOLECULAR LIBRARY; PHYSIOLOGY; PROTEIN QUATERNARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN SPUMARETROVIRUS;

BINDING SITES; CELL LINE; DATABASES, CHEMICAL; DIMERIZATION; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN STRUCTURE, QUATERNARY; PROTEIN STRUCTURE, TERTIARY; RNA, VIRAL; SMALL MOLECULE LIBRARIES; VIRUS REPLICATION;

EID: 84934904713     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0128310     Document Type: Article

References (74)

1. Dyda F, Hickman AB, Jenkins TM, Engelman A, Craigie R, Davies DR. Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science. 1994; 266(5193):1981-6. PMID: 7801124.
2. Jenkins TM, Engelman A, Ghirlando R, Craigie R. A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization. J Biol Chem. 1996; 271(13):7712-8. PMID: 8631811.
3. Wang JY, Ling H, Yang W, Craigie R. Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein. EMBO J. 2001; 20(24):7333-43. Epub 2001/12/18. doi: 10.1093/emboj/20.24.7333 PMID: 11743009; PubMed Central PMCID: PMC125787.
4. Li X, Krishnan L, Cherepanov P, Engelman A. Structural biology of retroviral DNA integration. Virology. 2011; 411(2):194-205. doi: S0042-6822(10)00752-X [pii] doi: 10.1016/j.virol.2010.12.008 PMID: 21216426.
5. Quashie PK, Sloan RD, Wainberg MA. Novel therapeutic strategies targeting HIV integrase. BMC medicine. 2012; 10:34. Epub 2012/04/14. doi: 10.1186/1741-7015-10-34 PMID: 22498430; PubMed Central PMCID: PMC3348091.
6. Engelman A, Liu Y, Chen H, Farzan M, Dyda F. Structure-based mutagenesis of the catalytic domain of human immunodeficiency virus type 1 integrase. J Virol. 1997; 71(5):3507-14. PMID: 9094622; PubMed Central PMCID: PMCPMC191497.
7. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science. 2000; 287(5453):646-50. doi: 8227 [pii]. PMID: 10649997.
8. Grobler JA, Stillmock K, Hu B, Witmer M, Felock P, Espeseth AS, et al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc Natl Acad Sci U S A. 2002; 99(10):6661-6. PMID: 11997448.
9. FDA. FDA approval of Isentress (raltegravir). Available: http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm124040.htm2007. [cited 2011 07/08/2011].
10. Serrao E, Odde S, Ramkumar K, Neamati N. Raltegravir, elvitegravir, and metoogravir: the birth of "metoo"HIV-1 integrase inhibitors. Retrovirology. 2009; 6:25. doi: 1742-4690-6-25 [pii] doi: 10.1186/1742-4690-6-25 PMID: 19265512; PubMed Central PMCID: PMCPMC2660292.
11. Goethals O, Clayton R, Van Ginderen M, Vereycken I, Wagemans E, Geluykens P, et al. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J Virol. 2008; 82(21):10366-74. doi: JVI.00470-08 [pii] doi: 10.1128/JVI.00470-08 PMID: 18715920; PubMed Central PMCID: PMCPMC2573211.
12. Dicker IB, Terry B, Lin Z, Li Z, Bollini S, Samanta HK, et al. Biochemical analysis of HIV-1 integrase variants resistant to strand transfer inhibitors. J Biol Chem. 2008; 283(35):23599-609. doi: M804213200 [pii] doi: 10.1074/jbc.M804213200 PMID: 18577511.
13. Blanco JL, Varghese V, Rhee SY, Gatell JM, Shafer RW. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis. 2011; 203(9):1204-14. doi: jir025 [pii] doi: 10.1093/infdis/jir025 PMID: 21459813; PubMed Central PMCID: PMCPMC3069732.
14. Hare S, Gupta SS, Valkov E, Engelman A, Cherepanov P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010; 464(7286):232-6. doi: nature08784 [pii] doi: 10.1038/nature08784 PMID: 20118915; PubMed Central PMCID: PMCPMC2837123.
15. Maertens GN, Hare S, Cherepanov P. The mechanism of retroviral integration from X-ray structures of its key intermediates. Nature. 2010; 468(7321):326-9. doi: nature09517 [pii] doi: 10.1038/nature09517 PubMed Central PMCID: PMCPMC2999894. PMID: 21068843
16. Hare S, Smith SJ, Métifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, et al. Structural and Functional Analyses of the Second-Generation Integrase Strand Transfer Inhibitor Dolutegravir (S/GSK1349572). Mol Pharmacol. 2011; 80(4):565-72. doi: mol.111.073189 [pii] doi: 10.1124/mol.111.073189 PMID: 21719464.
17. Hare S, Maertens GN, Cherepanov P. 3′-processing and strand transfer catalysed by retroviral integrase in crystallo. EMBO J. 2012; 31(13):3020-8. Epub 2012/05/15. doi: 10.1038/emboj.2012.118 PMID: 22580823; PubMed Central PMCID: PMC3395085.
18. Koltun WL. Precision space-filling atomic models. Biopolymers. 1965; 3(6):665-79. Epub 1965/12/01. doi: 10.1002/bip.360030606 PMID: 4158989.
19. Krishnan L, Li X, Naraharisetty HL, Hare S, Cherepanov P, Engelman A. Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc Natl Acad Sci U S A. 2010; 107(36):15910-5. doi: 1002346107 [pii] doi: 10.1073/pnas.1002346107 PMID: 20733078; PubMed Central PMCID: PMCPMC2936642.
20. Johnson BC, Metifiot M, Ferris A, Pommier Y, Hughes SH. A homology model of HIV-1 integrase and analysis of mutations designed to test the model. J Mol Biol. 2013; 425(12):2133-46. Epub 2013/04/02. doi: 10.1016/j.jmb.2013.03.027 PMID: 23542006.
21. Kessl JJ, Li M, Ignatov M, Shkriabai N, Eidahl JO, Feng L, et al. FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75. Nucleic Acids Res. 2011; 39(20):9009-22. doi: gkr581 [pii] doi: 10.1093/nar/gkr581 PMID: 21771857; PubMed Central PMCID: PMCPMC3203615.
22. Quashie PK, Mesplede T, Han YS, Oliveira M, Singhroy DN, Fujiwara T, et al. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol. 2012; 86(5):2696-705. Epub 2011/12/30. doi: 10.1128/JVI.06591-11 PMID: 22205735; PubMed Central PMCID: PMC3302270.
23. Mesplede T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, et al. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013; 10:22. Epub 2013/02/26. doi: 10.1186/1742-4690-10-22 PMID: 23432922; PubMed Central PMCID: PMC3598531.
24. Quashie PK, Mesplede T, Han YS, Veres T, Osman N, Hassounah S, et al. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother. 2013. Epub 2013/10/02. doi: 10.1128/AAC.01835-13 PMID: 24080645.
25. Mesplede T, Osman N, Wares M, Quashie PK, Hassounah S, Anstett K, et al. Addition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity. J Antimicrob Chemother. 2014. Epub 2014/06/12. doi: 10.1093/jac/dku199 PMID: 24917583.
26. Buenavista MT, Roche DB, McGuffin LJ. Improvement of 3D protein models using multiple templates guided by single-template model quality assessment. Bioinformatics. 2012; 28(14):1851-7. Epub 2012/05/18. doi: 10.1093/bioinformatics/bts292 PMID: 22592378.
27. Soding J, Biegert A, Lupas AN. The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 2005; 33(Web Server issue):W244-8. Epub 2005/06/28. doi: 10.1093/nar/gki408 PMID: 15980461; PubMed Central PMCID: PMC1160169.
28. Kelley L, Sternberg M. Protein structure prediction on the Web: a case study using the Phyre server. Nature Protocols. 2009; 4(3):363-71. doi: 10.1038/nprot.2009.2 PMID: ISI:000265782000009.
29. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics. 2008; 9:40. Epub 2008/01/25. doi: 10.1186/1471-2105-9-40 PMID: 18215316; PubMed Central PMCID: PMC2245901.
30. Baldi P, Chauvin Y. Protein modeling with hybrid Hidden Markov Model/neural network architectures. Proceedings / International Conference on Intelligent Systems for Molecular Biology; ISMB International Conference on Intelligent Systems for Molecular Biology. 1995; 3:39-47. Epub 1995/01/01. PMID: 7584463.
31. Soding J. Protein homology detection by HMM-HMM comparison. Bioinformatics. 2005; 21(7):951-60. Epub 2004/11/09. doi: 10.1093/bioinformatics/bti125 PMID: 15531603.
32. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, et al. Pfam: the protein families database. Nucleic Acids Res. 2014; 42(Database issue):D222-30. Epub 2013/11/30. doi: 10.1093/nar/gkt1223 PMID: 24288371; PubMed Central PMCID: PMC3965110.
33. Letunic I, Copley RR, Schmidt S, Ciccarelli FD, Doerks T, Schultz J, et al. SMART 4.0: towards genomic data integration. Nucleic Acids Res. 2004; 32(Database issue):D142-4. Epub 2003/12/19. doi: 10.1093/nar/gkh088 PMID: 14681379; PubMed Central PMCID: PMC308822.
34. Schultz J, Milpetz F, Bork P, Ponting CP. SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci U S A. 1998; 95(11):5857-64. Epub 1998/05/30. PMID: 9600884; PubMed Central PMCID: PMC34487.
35. Murzin AG, Brenner SE, Hubbard T, Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995; 247(4):536-40. Epub 1995/04/07. doi: 10.1006/jmbi.1995.0159 PMID: 7723011.
36. Sussman J, Lin D, Jiang J, Manning N, Prilusky J, Ritter O, et al. Protein Data Bank (PDB): Database of three-dimensional structural information of biological macromolecules. Acta Crystallographica Section D-Biological Crystallography. 1998; 54:1078-84. PMID: ISI:000077511400004.
37. Roy A, Kucukural A, Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010; 5(4):725-38. Epub 2010/04/03. doi: 10.1038/nprot.2010.5 PMID: 20360767; PubMed Central PMCID: PMC2849174.
38. Yang JY, Yan RX, Roy A, Xu D, Poisson J, Zhang Y. The I-TASSER Suite: protein structure and function prediction. Jcr-J Clin Rheumatol. 2015; 21(1):7-8. doi: 10.1038/Nmeth.3213 PMID: ISI:000346993500004.
39. Eswar N, Eramian D, Webb B, Shen MY, Sali A. Protein structure modeling with MODELLER. Methods Mol Biol. 2008; 426:145-59. Epub 2008/06/11. doi: 10.1007/978-1-60327-058-8-8 PMID: 18542861.
40. Chen JC, Krucinski J, Miercke LJ, Finer-Moore JS, Tang AH, Leavitt AD, et al. Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc Natl Acad Sci U S A. 2000; 97(15):8233-8. Epub 2000/07/13. doi: 10.1073/pnas.150220297 PMID: 10890912; PubMed Central PMCID: PMC26930.
41. Eisenberg D, Luthy R, Bowie JU. VERIFY3D: assessment of protein models with three-dimensional profiles. Methods in enzymology. 1997; 277:396-404. Epub 1997/01/01. PMID: 9379925.
42. Melo F, Devos D, Depiereux E, Feytmans E. ANOLEA: a www server to assess protein structures. Proceedings / International Conference on Intelligent Systems for Molecular Biology; ISMB International Conference on Intelligent Systems for Molecular Biology. 1997; 5:187-90. Epub 1997/01/01. PMID: 9322034.
43. Bowie JU, Luthy R, Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991; 253(5016):164-70. Epub 1991/07/12. PMID: 1853201.
44. Melo F, Feytmans E. Assessing protein structures with a non-local atomic interaction energy. J Mol Biol. 1998; 277(5):1141-52. Epub 1998/05/22. doi: 10.1006/jmbi.1998.1665 PMID: 9571028.
45. Ramachandran GN, Ramakrishnan C, Sasisekharan V. Stereochemistry of polypeptide chain configurations. J Mol Biol. 1963; 7:95-9. Epub 1963/07/01. PMID: 13990617.
46. Dunbrack RL Jr., Karplus M. Conformational analysis of the backbone-dependent rotamer preferences of protein sidechains. Nature structural biology. 1994; 1(5):334-40. Epub 1994/05/01. PMID: 7664040.
47. Wang Q, Canutescu AA, Dunbrack RL, Jr. SCWRL and MolIDE: computer programs for side-chain conformation prediction and homology modeling. Nat Protoc. 2008; 3(12):1832-47. Epub 2008/11/08. doi: 10.1038/nprot.2008.184 PMID: 18989261; PubMed Central PMCID: PMC2682191.
48. Prlic A, Bliven S, Rose PW, Bluhm WF, Bizon C, Godzik A, et al. Pre-calculated protein structure alignments at the RCSB PDB website. Bioinformatics. 2010; 26(23):2983-5. Epub 2010/10/13. doi: 10.1093/bioinformatics/btq572 PMID: 20937596; PubMed Central PMCID: PMC3003546.
49. The PyMOL Molecular Graphics System, Version 1.3, Schrödinger, LLC.
50. Irwin JJ, Shoichet BK. ZINC - a free database of commercially available compounds for virtual screening. Journal of chemical information and modeling. 2005; 45(1):177-82. Epub 2005/01/26. doi: 10.1021/ci049714+ PMID: 15667143; PubMed Central PMCID: PMC1360656.
51. Dallakyan S, Olson AJ. Small-Molecule Library Screening by Docking with PyRx. Methods Mol Biol. 2015; 1263:243-50. Epub 2015/01/27. doi: 10.1007/978-1-4939-2269-7-19 PMID: 25618350.
52. Trott O, Olson A. Software News and Update AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. Journal of Computational Chemistry. 2010; 31(2):455-61. doi: 10.1002/jcc.21334 PMID: ISI:000273412900020.
53. Xu HT, Asahchop EL, Oliveira M, Quashie PK, Quan Y, Brenner BG, et al. Compensation by the E138K Mutation in HIV-1 Reverse Transcriptase of Deficits in Viral Replication Capacity and Enzyme Processivity Associated with the M184I/V Mutations. J Virol. 2011. doi: JVI.05584-11 [pii] doi: 10.1128/JVI.05584-11. PMID: 21849444.
54. Kramer VG, Schader SM, Oliveira M, Colby-Germinario SP, Donahue DA, Singhroy DN, et al. Maraviroc and other HIV-1 entry inhibitors exhibit a class-specific redistribution effect that results in increased extracellular viral load. Antimicrob Agents Chemother. 2012; 56(8):4154-60. Epub 2012/05/23. doi: 10.1128/AAC.00409-12 PMID: 22615275; PubMed Central PMCID: PMC3421589.
55. Han YS, Quashie P, Mesplede T, Xu H, Mekhssian K, Fenwick C, et al. A high-throughput assay for HIV-1 integrase 3′-processing activity using time-resolved fluorescence. Journal of virological methods. 2012; 184(1-2):34-40. Epub 2012/05/16. doi: 10.1016/j.jviromet.2012.05.003 PMID: 22584270.
56. Han YS, Xiao WL, Quashie PK, Mesplede T, Xu H, Deprez E, et al. Development of a fluorescence-based HIV-1 integrase DNA binding assay for identification of novel HIV-1 integrase inhibitors. Antiviral Res. 2013; 98(3):441-8. Epub 2013/04/16. doi: 10.1016/j.antiviral.2013.04.001 PMID: 23583286.
57. Yan H, Mizutani TC, Nomura N, Takakura T, Kitamura Y, Miura H, et al. A novel small molecular weight compound with a carbazole structure that demonstrates potent human immunodeficiency virus type-1 integrase inhibitory activity. Antiviral chemistry & chemotherapy. 2005; 16(6):363-73. Epub 2005/12/07. PMID: 16329284.
58. Zhang Y. I-TASSER: fully automated protein structure prediction in CASP8. Proteins. 2009; 77 Suppl 9:100-13. doi: 10.1002/prot.22588 PMID: 19768687; PubMed Central PMCID: PMCPMC2782770.
59. Seeliger D, de Groot B. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. Journal of Computer-Aided Molecular Design. 2010; 24(5):417-22. doi: 10.1007/s10822-010-9352-6 PMID: ISI:000278469700004.
60. Bonnenfant S, Thomas CM, Vita C, Subra F, Deprez E, Zouhiri F, et al. Styrylquinolines, integrase inhibitors acting prior to integration: a new mechanism of action for anti-integrase agents. J Virol. 2004; 78(11):5728-36. Epub 2004/05/14. doi: 10.1128/JVI.78.11.5728-5736.2004 PMID: 15140970; PubMed Central PMCID: PMC415813.
61. Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, Perno CF. Characterization and structural analysis of HIV-1 integrase conservation. AIDS reviews. 2009; 11(1):17-29. Epub 2009/03/18. PMID: 19290031.
62. Kessl JJ, McKee CJ, Eidahl JO, Shkriabai N, Katz A, Kvaratskhelia M. HIV-1 Integrase-DNA Recognition Mechanisms. Viruses. 2009; 1(3):713-36. Epub 2009/12/01. doi: 10.3390/v1030713 PMID: 21994566; PubMed Central PMCID: PMC3185514.
63. Mousnier A, Leh H, Mouscadet JF, Dargemont C. Nuclear import of HIV-1 integrase is inhibited in vitro by styrylquinoline derivatives. Mol Pharmacol. 2004; 66(4):783-8. Epub 2004/07/13. doi: 10.1124/mol.104.001735 PMID: 15247318.
64. Rhodes DI, Peat TS, Vandegraaff N, Jeevarajah D, Le G, Jones ED, et al. Structural basis for a new mechanism of inhibition of HIV-1 integrase identified by fragment screening and structure-based design. Antiviral chemistry & chemotherapy. 2011; 21(4):155-68. Epub 2011/05/24. doi: 10.3851/IMP1716 PMID: 21602613.
65. Levin A, Hayouka Z, Friedler A, Loyter A. Transportin 3 and importin α are required for effective nuclear import of HIV-1 integrase in virus-infected cells. Nucleus. 2010; 1(5):422-31. doi: 10.4161/nucl.1.5.12903 PMID: 21326825; PubMed Central PMCID: PMCPMC3037538.
66. Sun R, Song HC, Wang CR, Shen KZ, Xu YB, Gao YX, et al. Compounds from Kadsura angustifolia with anti-HIV activity. Bioorg Med Chem Lett. 2011; 21(3):961-5. Epub 2011/01/15. doi: 10.1016/j.bmcl.2010.12.055 PMID: 21232955.
67. Quashie PK, Oliviera M, Veres T, Osman N, Han YS, Hassounah S, et al. Differential effects of the G118R, H51Y and E138K resistance substitutions in HIV integrase of different subtypes. J Virol. 2014. Epub 2015/01/02. doi: 10.1128/JVI.03353-14 PMID: 25552724.
68. De Luca L, Ferro S, Morreale F, De Grazia S, Chimirri A. Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75. ChemMedChem. 2011; 6(7):1184-91. doi: 10.1002/cmdc.201100071 PMID: 21506277.
69. Christ F, Voet A, Marchand A, Nicolet S, Desimmie BA, Marchand D, et al. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol. 2010; 6(6):442-8. doi: nchembio.370 [pii] doi: 10.1038/nchembio.370 PMID: 20473303.
70. Desimmie BA, Schrijvers R, Demeulemeester J, Borrenberghs D, Weydert C, Thys W, et al. LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions. Retrovirology. 2013; 10:57. Epub 2013/06/01. doi: 10.1186/1742-4690-10-57 PMID: 23721378; PubMed Central PMCID: PMC3671127.
71. Schrijvers R, De Rijck J, Demeulemeester J, Adachi N, Vets S, Ronen K, et al. LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs. PLoS Pathog. 2012; 8(3):e1002558. Epub 2012/03/08. doi: 10.1371/journal.ppat.1002558 PMID: 22396646; PubMed Central PMCID: PMC3291655.
72. Di Tommaso P, Moretti S, Xenarios I, Orobitg M, Montanyola A, Chang JM, et al. T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension. Nucleic Acids Res. 2011; 39(Web Server issue):W13-7. Epub 2011/05/12. doi: 10.1093/nar/gkr245 PMID: 21558174; PubMed Central PMCID: PMC3125728.
73. Wainberg MA, Mesplede T, Quashie PK. The development of novel HIV integrase inhibitors and the problem of drug resistance. Current opinion in virology. 2012; 2(5):656-62. Epub 2012/09/20. doi: 10.1016/j.coviro.2012.08.007 PMID: 22989757.
74. Mesplede T, Quashie PK, Wainberg MA. Resistance to HIV integrase inhibitors. Current opinion in HIV and AIDS. 2012; 7(5):401-8. Epub 2012/07/14. doi: 10.1097/COH.0b013e328356db89 PMID: 22789986.