discovery and development of hiv 1 entry inhibitors that target gp120

... 0. 01 ml 3,1E+05 1, E+06 1, E+05 1, E+04 1, E+03 1, E+02 1, E+ 01 1,E+00 FLY -HIV- 87-GFP FLY-syn-GFP Figure MLV /HIV- 1 pseudotyped vector particles released from producer cells Titer of Titer of MLV /HIV- 1 ... Evaluation of HIV- 1 entry inhibitors Attachment and entry of HIV- 1 into CD4 cells involve a series of conformational changes in Env which allow coreceptor binding and finally fusion of viral and cell ... CCR5 for entry The transfer of a marker gene by MLV/ HIV- 1 vectors is therefore a safe and simple method to assay entry mediated by HIV- 1 Env and can be used to evaluate HIV- 1 entry inhibitors, ...

Ngày tải lên: 10/08/2014, 05:20

... Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type with Zidovudine Treatment N Engl J Med 19 94, 3 31( 18) :11 73 -11 80 Abrams EJ: Prevention of mother-to-child transmission of HIV ... passage of HIV- 1 across a monolayer of BeWo cells by virus infected PBMCs Our data show that CCR5 and fusion inhibitors, in one hand, and the CXCR4 antagonist AMD 310 0, in the other hand, efficiently ... serum and 10 0 IU/ml of recombinant human IL-2 (Chiron B.V Amsterdam, The Netherlands) Viruses The viral isolate HIV- 1 Ba-L (R5), a primary isolate of HIV1 LAI (X4), the clinical isolate HIV- 1 A204...

Ngày tải lên: 13/08/2014, 05:20

... Neam-r9 Neo-r9 R9 997 .17 8 13 01. 523 15 93.809 14 65.742 17 70.076 2062.362 14 65. 710 997. 61 13 01. 80 15 94 .14 14 66.00 17 70.43 2063.00 14 66 .13 Table Antiviral activity of L-APACs against HIV- 1IIIB virus ND, ... 4.9 2.2 4.0 1. 4 2.4 1. 5 6.8 6.2 4.8 2.0 6.0 2.8 8.0 3.2 5.7 2.2 5 .1 2 .1 5.3 1. 7 3.0 1. 6 2.7 1. 2 ND 13 .9 2.7 ND 9.7 1. 9 ND 2.9 1. 3 ND 4.3 1. 3 17 0 15 0 15 5 15 0 15 0 12 0 ± ± ± ± ± ± 1. 0 0.4 1. 0 0.6 0.4 ... Paramo-R9 Neo-R9 Neam-R ⁄ r9a R9-Ac Neo-mycin 11 0 ± 20 ND 70 ± 10 210 31 ± 10 16 0 40 ± 12 200 33 ± 12 0 37.5 ± 2.5 17 5 31 ± 14 0 30 ± 15 0 28 ± 16 0 31 ND > 200 > 300 a Neam-RRrRrRrRR d ⁄ l-9-mer-arginine...

Ngày tải lên: 16/03/2014, 06:20

... B of the complex of HIV- 1 protease with OE inhibitor 0.05 11 21 31 41 51 61 71 91 81 Residue number B factor 80 chain A 60 40 20 0 11 21 31 41 51 61 71 81 91 20 40 chain B Fig The complex of HIV- 1 ... hydrogen bonds to the Asp29 S3¢ OE I50 A128 D129 D130 V132 I147 G148 RE SE – 14 – – 2 11 – – 31 18 23 OE R8 D129 G148 G149 F153 RE SE 1 13 – 1 11 – 22 20 13 ˚ and Asp30 with bond-length differences ... S1 17 17 OE G27 G48 G49 I50 L123 P1 81 V182 RE SE – 1 5 – – – 17 16 12 S2¢ OE L23 D25 T80 P 81 V82 I84 G127 G149 I150 RE SE – 1 7 26 – 1 – 31 – – 19 from the catalytic aspartates at the bottom of...

Ngày tải lên: 19/02/2014, 16:20

... superposition of unliganded C95M/C1095A structure with each of the six cyclic urea-complexed structures shown in Fig 2B 1LV1 1LV1 1HWR 1DMP 1QBS 1HVR 1QBR 1QBT 1HWR 1DMP 1QBS 1HVR 1QBR 1QBT 0.00 ... 1HVR, 1QBS, 1DMP, 1QBR and 1QBT) are of complexes between different types of inhibitor molecules and HIV- 1 protease containing the C95A mutation In two of these structures (1DAZ and 1A94), the ... D.A., Sharpe, T.R & Erickson-Viitanen, S (19 94) Rational design of potent, 12 13 14 15 16 17 18 bio-available, non-peptide cyclic ureas as HIV- 1 protease inhibitors Science 263, 380–384 Lam, P.Y.,...

Ngày tải lên: 31/03/2014, 07:20

... 2002, 18 6: 617 -625 Abstract Page of (page number not for citation purposes) Journal of the International AIDS Society 2005, 7: 71 10 11 12 13 14 15 http://www.jiasociety.org/content/7 /1/ 71 Kantor ... analyses of RT and protease sequences from persons infected with nonsubtype B HIV- 1 Program and abstracts of the 10 th Conference on Retroviruses and Opportunistic Infections; February 10 14, 2003; ... analysis of RT and protease sequences and data from persons infected with non-B HIV- 1 subtypes Currently, the workgroup consists of investigators from 15 sites in 13 countries The goal of the workgroup...

Ngày tải lên: 20/06/2014, 08:20

... Acad Sci USA 2003, 10 0 :18 3 -18 8 Page 10 of 11 (page number not for citation purposes) AIDS Research and Therapy 2004, 1: 2 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Anderson J, Banerjea ... Research and Therapy 2004, 1: 2 http://www.aidsrestherapy.com/content /1/ 1/2 Figure HIV- 1 challenge of differentiated macrophages HIV- 1 challenge of differentiated macrophages: HIV- 1 Tar, Tar-CCR5Rz and ... transduction and sustained expression of HIV- 1 interfering genes, anti-CCR5 ribozyme and HIV- 1 Page of 11 (page number not for citation purposes) AIDS Research and Therapy 2004, 1: 2 http://www.aidsrestherapy.com/content /1/ 1/2...

Ngày tải lên: 10/08/2014, 05:20

... 80e, 1HSC+, 50f) 10 0 10 0 .1 0. 01 0.0 01 % of population 10 0 % of population 10 0 % of population Years D S4 (6x, 0.0 01 Years 0 .1 0. 01 0.0 01 11 13 11 13 0 .1 0. 01 11 13 Years Years G 0.0 01 Years H S10 ... 10 0 10 10 10 0 .1 0. 01 0.0 01 % of population 10 0 % of population % of population 10 0 0 .1 0. 01 0.0 01 11 13 0 .1 0. 01 11 13 11 13 Years E F 60e, 20HSC+, 99f) S6 (2x, S7 (2x, 80e, 20HSC+, 50f) 10 10 ... 90f) S 11 (6x, 10 80e, 20HSC+, 99f, C-II) 10 0 10 % of population 10 0 % of population 80e, 20HSC+, 99f) 0 .1 0. 01 0.0 01 Cell status Tx wt Tx m = Tx m = UNTx wt UNTx m = UNTx m = 0 .1 0. 01 0.0 01 11 13...

Ngày tải lên: 13/08/2014, 01:20

... 203 1. 1 0.85 -1. 46 0. 417 10 4 1. 1 0.77 -1. 56 0. 61 99 1. 2 0.75 -1. 75 0.5 31 HHD 16 7 1. 0 0.74 -1. 32 0.983 94 0.9 0.59 -1. 23 0.385 73 1. 2 0.75 -1. 92 0.442 HHE HHD/HHE 15 8 31 1 .1 1.9 0.82 -1. 51 1 .14 -3 .16 0.495 ... (15 .9) 75 (15 .6) 10 5 (16 .1) HHE 310 (13 .7) 13 8 (12 .2) 17 2 (15 .2) 61 (12 .7) 11 1 (17 .0) HHF *1 128 (5.6) 76 (6.7) 52 (4.6) 24 (5.0) 28 (4.3) HHF*2 480 ( 21. 2) 259 (22.8) 2 21 (19 .5) 99 (20.6) 12 2 (18 .7) ... HHA 6 01 (26.5) 305 (26.9) 296 (26 .1) 13 3 (27.7) 16 3 (24.9) HHB HHC 44 (1. 9) 17 8 (7.9) 25 (2.2) 69 (6 .1) 19 (1. 7) 10 9 (9.6) (1. 7) 42 (8.8) 11 (1. 7) 67 (10 .2) HHD 370 (16 .3 19 0 (16 .8) 18 0 (15 .9)...

Ngày tải lên: 13/08/2014, 01:20

... interests Page of 14 15 16 17 18 19 20 21 Received: 20 April 2 011 Accepted: June 2 011 Published: June 2 011 References Chan DC, Fass D, Berger JM, Kim PS: Core structure of gp 41 from the HIV envelope ... in the CD4 binding cavity of HIV- 1 gp120 influencing gp120- CD4 interactions and fusogenicity of HIV- 1 envelopes derived from brain and other tissues Retrovirology 2 011 8:42 Submit your next manuscript ... the HIV gp120 envelope glycoprotein Nature 19 98, 393:705- 711 12 Wyatt R, Sodroski J: The HIV- 1 envelope glycoproteins: fusogens, antigens, and immunogens Science 19 98, 280 :18 84 -18 88 13 Sterjovski...

Ngày tải lên: 13/08/2014, 01:20

... V370A HXB2 - 2.8 > 15 0 6.6 > 15 0 PR -1 (20R-36I-54V-63P-71I-82T) 0.6 2 .1 > 15 0 6.0 > 15 0 PR-2 (431V -10 I -13 V-36I-46I-54V-62V-63P-71T-82A-90M-93L) 2 .1 > 15 0 > 15 0 > 15 0 > 15 0 Levels of bevirimat resistance ... JM, Richman DD: Update of the drug resistance mutations in HIV- 1: December 2 010 Top HIV Med 2 010 , 18 :15 6 -16 3 doi :10 .11 86 /17 42-4690-8-70 Cite this article as: Fun et al.: HIV- 1 protease inhibitor ... 12 .2 5.6 15 .1 7.8 PR-2 431V 3I -10 I -13 V-35D-36I-37D-46I-54V-55R-57K-62V-63P-71T-82A-90M-93L-95F # PR-3 431V 3I -10 I -13 V-35D-36I-37D-54V-55R-57K-62V-63P-71T-82A-90M-93L-95F > 12 0 > 12 0 PR-4# 431V...

Ngày tải lên: 13/08/2014, 01:21

... Page 11 of 13 (page number not for citation purposes) Retrovirology 2008, 5:72 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 innate immunity to retroviral infection Cell 2003, 11 3(6):803-809 ... Vif(-) HIV- 1NL4-3 P24 antigen was measured post-infected day 3, 5, 7, 10 14 , 21 a results of wild type Vif(+) HIV- 1NL4-3 infection; b results of Vif(-) HIV- 1NL4-3 Δ Vif infection Page of 13 (page ... packaging J Virol 2004, 78( 21) :11 8 41- 118 52 Schafer A, Bogerd HP, Cullen BR: Specific packaging of APOBEC3G into HIV- 1 virions is mediated by the nucleocapsid domain of the gag polyprotein precursor...

Ngày tải lên: 13/08/2014, 05:21

... Mol Cell Biol 19 91, 11 :16 24 -16 30 Gilmartin GM, Fleming ES, Oetjen J: Activation of HIV- 1 premRNA 3' processing in vitro requires both an upstream element and TAR EMBO J 19 92, 11 :4 419 -4428 Valsamakis ... declare that they have no competing interests 12 13 14 15 16 17 18 Authors' contributions 19 MMV and AH performed the experiments MMV drafted the manuscript ATD and BB designed the experiments and ... AB Δ39-48 11 -24 Δ39-48 TARwt HIV- LAI TARm HIV- rtTA 11 -24 Figure The HIV- rtTA genome and mutations in the TAR hairpin The HIV- rtTA genome and mutations in the TAR hairpin (A) The HIV- rtTA proviral...

Ngày tải lên: 13/08/2014, 05:21

... Page of 15 (page number not for citation purposes) Retrovirology 2007, 4: 21 A http://www.retrovirology.com/content/4 /1/ 21 B E152 E152 N155 T66 D64 D 116 D64 D 116 T66 D C D 116 E152 N155 D 116 E152 ... (10 ) -1 Log IC50 (strand transfer) styrylquinoline KHD1 61 (11 ) primaquine (12 ) chloroquine (13 ) quinacrine (14 ) dihydroxypydimidine carboxamide (15 ) MK-0 518 (16 ) equisetin (17 ) oteromycin (18 ) ... with a RMSD of 0.24 Å between the α-carbons of the highly conserved catalytic triads (D64, D1 21 and E157 for RSV IN) The position of the metal ion between D64 and D 116 of HIV- 1 IN and the metal...

Ngày tải lên: 13/08/2014, 09:20

... Provider 10 1. 4 Problem Statement 14 1. 5 Approaches and Contributions 16 1. 5 .1 The Service Management Layer: LASPD 17 1. 5.2 The ... layers for the provision, discovery, and development of ubiquitous services and applications As a proof of concept, we demonstrate the use of the framework for the development of an information sharing ... 10 8 Context Constraint Specification 11 1 ACE: Application Independent Engine for Application Context Realization 112 4.3 .1 4.3.2 Context Fact Management 11 7...

Ngày tải lên: 10/09/2015, 08:36

... Tazi et al HIV- 1 alternative splicing regulation Fig Organization of HIV- 1 genome and different mRNA splicing products The 5¢ss (D1–D4) and 3¢ss (A1–A7) are indicated ORFs of coding exons of each ... binding of U2AF The lower panel shows that most of the HIV- 1 3¢ss deviate from the consensus because of their low content of pyrimidine nucleotides virus production [16 ,27] (Fig 5, Table 1) HIV- 1 replication ... addition, hnRNP E1 ⁄ E2 are also able to interact with an HIV- 1 segment including the ESS3 element in tat ⁄ rev exon of HIV- 1 and modulation of hnRNP E1 expression alters HIV- 1 protein synthesis...

Ngày tải lên: 06/03/2014, 09:22

... 1. 87 1. 81 1.87 1. 81 1.87 1. 81 2 .18 –2 .10 2.07–2.00 1. 97 1. 90 24.6 1. 81 19.0 21. 8 16 77 24.0–2.30 18 .1 20.0 16 62 24.6–2. 01 18.0 20.3 16 47 27.9 1. 81 18.8 222.4 16 97 22.6 1. 81 19.4 23.4 16 94 15 .0 1. 81 ... of inhibitor/ protease contacts Ki (nM) 642.7 91 652.743 633.740 636.743 610 .705 663 .14 1 778.977 768.908 768.908 14 00.48 14 26.56 13 69 .16 13 94.59 13 98.39 13 91. 54 15 28. 61 1572 .11 15 51. 03 11 10 10 ... 58 .12 86 .11 46 .11 2 .10 35374 13 120 93 .1 7.5 77 .1 63 .1 58.48 86.67 46.52 2.00 44926 15 612 92.9 11 .6 72.5 61. 0 58.89 86.70 46.70 1. 90 623 91 18784 95.7 8 .1 90.4 79.2 1. 86 1. 80 2.40–2.30 2.07–2.00 1. 87 1. 81...

Ngày tải lên: 08/03/2014, 02:20

... 0.48 0. 31 Sinsi -11 .16 0. 01 0.04 SE 0. 31 AP .18 /18 2, 18 3 AP.2/221A AP.28/282, 284 AP.33/3 31, 334 AP.4/452, 454 AP.5/ 512 , 514 AP.6/639 AP .10 /10 11, 10 14 A score of -6.96 was used as a cut off for ... 210 1 (B-X4/R5) 30 41 (C-R5) 54 41 (C-X4) MAGI-CXCR4 10 000 5000 No of blue cells 21 23 9 13 23 1 11 16 - 10 000 Phenotype from MT-2 No of blue cells 99 92 18 12 30 31 65 26 33 19 10 34 - 10 23 21 ... monocytes/macrophages and other cell types [11 ,14 ,15 ] to enter target cells Analysis of env gp120 sequences from a large number of HIV- 1 isolates shows that gp120 is made up of five variable regions (V1 to V5) that...

Ngày tải lên: 18/06/2014, 18:20

... 0.48 0. 31 Sinsi -11 .16 0. 01 0.04 SE 0. 31 AP .18 /18 2, 18 3 AP.2/221A AP.28/282, 284 AP.33/3 31, 334 AP.4/452, 454 AP.5/ 512 , 514 AP.6/639 AP .10 /10 11, 10 14 A score of -6.96 was used as a cut off for ... 210 1 (B-X4/R5) 30 41 (C-R5) 54 41 (C-X4) MAGI-CXCR4 10 000 5000 No of blue cells 21 23 9 13 23 1 11 16 - 10 000 Phenotype from MT-2 No of blue cells 99 92 18 12 30 31 65 26 33 19 10 34 - 10 23 21 ... monocytes/macrophages and other cell types [11 ,14 ,15 ] to enter target cells Analysis of env gp120 sequences from a large number of HIV- 1 isolates shows that gp120 is made up of five variable regions (V1 to V5) that...

Ngày tải lên: 20/06/2014, 01:20

... http://www.virologyj.com/content/5 /1/ 56 17 References 10 11 12 13 14 15 16 Alkhatib G, Berger EA: HIV coreceptors: from discovery and designation to new paradigms and promise European journal of medical research 2007, 12 (9):375-384 ... gp 41 R5 HIV gp120 CD4 Cell Membrane CCR5 C D X4 HIV X4 HIV CXCR4 Figure Proposed model of the mechanism of action of BFFI Proposed model of the mechanism of action of BFFI The fusion process of ... time of action of different classes of entry inhibitors As expected, CCR5mAb maximally inhibited HIV entry at an early stage (t1/2 = 18 min) and T2635 inhibited HIV entry at a late stage (t1/2...

Ngày tải lên: 20/06/2014, 01:20