The binding mode of fusion inhibitor T20 onto HIV-1 gp41 and relevant T20-resistant mechanisms explored by computational study

Current HIV Research

Volumn 10, Issue 2, 2012, Pages 182-194

  Qiu, Su ^a   Yi, Hong ^a   Hu, Jun ^a   Cao, Zhijian ^a   Wu, Yingliang ^a   Li, Wenxin ^a  

^a WUHAN UNIVERSITY   (China)

Author keywords

Conformational dynamics; Enfuvirtide (T20); Fusion peptide (FP); HIV 1 envelop protein gp41; Molecular dynamics simulation (MDS); Resistance mutation; Trimetric helices

Indexed keywords

ENFUVIRTIDE; GLYCOPROTEIN GP 41; PHENYLALANINE; TRYPTOPHAN;

ANTIVIRAL ACTIVITY; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG PROTEIN BINDING; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR DYNAMICS; MUTATION; NONHUMAN; PROTEIN STRUCTURE; SIMULATION;

DRUG RESISTANCE, VIRAL; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV-1; HUMANS; MODELS, THEORETICAL; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

EID: 84860276384     PISSN: 1570162X     EISSN: 18734251     Source Type: Journal    
DOI: 10.2174/157016212799937191     Document Type: Article

References (51)

1. Lawless MK, Barney S, Guthrie KI, Bucy TB, Petteway SR, Jr. Merutka G. HIV-1 membrane fusion mechanism: structural studies of the interactions between biologically-active peptides from gp41. Biochemistry 1996; 35: 13697-708.
2. Chan DC, Kim PS. HIV entry and its inhibition. Cell 1998; 93: 681-4.
3. Kliger Y, Shai Y. Inhibition of HIV-1 entry before gp41 folds into its fusion-active conformation. J Mol Biol 2000; 295: 163-8.
4. Este JA, Telenti A. HIV entry inhibitors. Lancet 2007; 370: 81-8.
5. Judice JK, Tom JY, Huang W, et al. Inhibition of HIV type 1 infectivity by constrained alpha-helical peptides: implications for the viral fusion mechanism. Proc Natl Acad Sci U S A 1997; 94: 13426-30.
6. Kliger Y, Peisajovich SG, Blumenthal R, Shai Y. Membrane-induced conformational change during the activation of HIV-1 gp41. J Mol Biol 2000; 301: 905-14.
7. Shu W, Ji H, Lu M. Interactions between HIV-1 gp41 core and detergents and their implications for membrane fusion. J Biol Chem 2000; 275: 1839-45.
8. Liu J, Shu W, Fagan MB, Nunberg JH, Lu M. Structural and functional analysis of the HIV gp41 core containing an Ile573 to Thr substitution: implications for membrane fusion. Biochemistry 2001; 40: 2797-807.
9. Zwick MB, Saphire EO, Burton DR. gp41: HIV's shy protein. Nat Med 2004; 10: 133-4.
10. Briz V, Poveda E, Soriano V. HIV entry inhibitors: mechanisms of action and resistance pathways. J Antimicrob Chemother 2006; 57: 619-27.
11. Reeves JD, Gallo SA, Ahmad N, et al. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/co receptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A 2002; 99: 16249-54.
12. Kilby JM, Eron JJ. Novel therapies based on mechanisms of HIV-1 cell entry. N Engl J Med 2003; 348: 2228-38.
13. Copeland KF. Inhibition of HIV-1 entry into cells. Recent Pat Anti infect Drug Discov 2006; 1: 107-12.
14. Krambovitis E, Spandidos DA. HIV-1 infection: is it time to reconsider our concepts? Int J Mol Med 2006; 18: 3-8.
15. Eckert DM, Kim PS. Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region. Proc Natl Acad Sci U S A 2001; 98: 11187-92.
16. Bewley CA, Louis JM, Ghirlando R, Clore GM. Design of a novel peptide inhibitor of HIV fusion that disrupts the internal trimeric coiledcoil of gp41. J Biol Chem 2002; 277: 14238-45.
17. Rabenstein MD, Shin YK. HIV-1 gp41 tertiary structure studied by EPR spectroscopy. Biochemistry 1996; 35: 13922-8.
18. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell 1997; 89: 263-73.
19. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387: 426-30.
20. Wild C, Greenwell T, Matthews T. A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 1993; 9: 1051-3.
21. Wild CT, Shugars DC, Greenwell TK, McDanal CB, Matthews TJ. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci U S A 1994; 91: 9770-4.
22. Shafer RW, Schapiro JM. HIV-1 drug resistance mutations: an updated framework for the second decade of HAART. AIDS Rev 2008; 10: 67-84.
23. Fletcher CV. Enfuvirtide, a new drug for HIV infection. Lancet 2003; 361: 1577-8.
24. Matthews T, Salgo M, Greenberg M, Chung J, DeMasi R, Bolognesi D. Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat Rev Drug Discov 2004; 3: 215-25.
25. Struble K, Murray J, Cheng B, Gegeny T, Miller V, Gulick R. Antiretroviral therapies for treatment-experienced patients: current status and research challenges. AIDS 2005; 19: 747-56.
26. Morse C, Maldarelli F. Enfuvirtide antiviral activity despite rebound viremia and resistance mutations: fitness tampering or a case of persistent braking on entering? J Infect Dis 2007; 195: 318-21.
27. Kilby JM, Hopkins S, Venetta TM, et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998; 4: 1302-7.
28. Trivedi VD, Cheng SF, Wu CW, Karthikeyan R, Chen CJ, Chang DK. The LLSGIV stretch of the N-terminal region of HIV-1 gp41 is critical for binding to a model peptide, T20. Protein Eng 2003; 16: 311-7.
29. Chang DK, Hsu CS. Biophysical evidence of two docking sites of the carboxyl heptad repeat region within the amino heptad repeat region of gp41 of human immunodeficiency virus type 1. Antiviral Res 2007; 74: 51-8.
30. Wei X, Decker JM, Liu H, et al. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002; 46: 1896-905.
31. Greenberg ML, Cammack N. Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 2004; 54: 333-40.
32. Lu J, Sista P, Giguel F, Greenberg M, Kuritzkes DR. Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). J Virol 2004; 78: 4628-37.
33. Mink M, Mosier SM, Janumpalli S, et al. Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol 2005; 79: 12447-54.
34. Nameki D, Kodama E, Ikeuchi M, et al. Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions. J Virol 2005; 79: 764-70.
35. Labrosse B, Morand-Joubert L, Goubard A, et al. Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients. J Virol 2006; 80: 8807-19.
36. Melby T, Sista P, DeMasi R, et al. Characterization of envelope glycoprotein gp41 genotype and phenotypic susceptibility to enfuvirtide at baseline and on treatment in the phase III clinical trials TORO-1 and TORO-2. AIDS Res Hum Retroviruses 2006; 22: 375-85.
37. Davison DK, Medinas, RJ, Mosier, SM, et al. New fusion inhibitor peptides, TRI-999 and TRI-1144, are potent inhibitors of enfuvirtide and T-1249 resistant isolates: Conference Reports for NATAP on XVI International AIDS Conference; Aug 2006; Poster THPE0021 2006.
38. Buzon V, Natrajan G, Schibli D, Campelo F, Kozlov MM, Weissenhorn W. Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions. PLoS Pathog 2010; 6: e1000880.
39. Udier-Blagović M, Tirado-Rives J, Jorgensen WL. Validation of a Model for the Complex of HIV-1 Reverse Transcriptase with Sustiva through Computation of Resistance Profiles. J Am Chem Soc 2000; 122: 12898-900.
40. Kroeger Smith MB, Hose BM, Hawkins A, et al. Molecular Modeling Calculations of HIV-1 Reverse Transcriptase Nonnucleoside Inhibitors: Correlation of Binding Energy with Biological Activity for Novel 2-Aryl-Substituted Benzimidazole Analogues. J Med Chem 2003; 46: 1940-47.
41. Trylska J, Tozzini V, Chang CE, McCammon JA. HIV-1 protease substrate binding and product release pathways explored with coarsegrained molecular dynamics. Biophys J 2007; 92: 4179-87.
42. Sousa SF, Tamames B, Fernandes PA, Ramos MJ. Detailed atomistic analysis of the HIV-1 protease interface, J Phys Chem B 2011; 115: 7045-57.
43. Lexa KW, Carlson HA. Binding to the open conformation of HIV-1 protease, Proteins 2011; 79: 2282-22890.
44. McGillick BE, Balius TE, Mukherjee S, Rizzo RC. Origins of resistance to the HIVgp41 viral entry inhibitor T20. Biochemistry 2010; 49: 3575-92.
45. Yi H, Cao Z, Yin S, Dai C, Wu Y, Li W. Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition. J Proteome Res 2007; 6: 611-620.
46. Qiu S, Yi H, Liu H, Cao Z, Wu Y, Li W. Molecular Information of charybdotoxin blockade in the large conductance calcium-activated potassium channel. J Chem Inf Model 2009; 49: 1831-1838.
47. Case DA, Darden TA, Cheatham TE, et al. Amber 8. San Francisco: University of California 2004.
48. Gordon LM, Mobley PW, Lee W, et al. Conformational mapping of the N-terminal peptide of HIV-1 gp41 in lipid detergent and aqueous environments using 13C-enhanced Fourier transform infrared spectroscopy. Protein Sci 2004; 13: 1012-30.
49. Jaroniec CP, Kaufman JD, Stahl SJ, et al. Structure and dynamics of micelle-associated human immunodeficiency virus gp41 fusion domain. Biochemistry 2005; 44: 16167-16180.
50. Sackett K, Wexler-Cohen Y, Shai Y. Characterization of the HIV Nterminal fusion peptide-containing region in context of key gp41 fusion conformations. J Biol Chem 2006; 281: 21755-21762.
51. Johnson VA, Brun-Vezinet F, Clotet B, et al. Update of the drug resistance mutations in HIV-1: 2007. Top HIV Med 2007; 15: 119-125.