A phenyl-thiadiazolylidene-amine derivative ejects zinc from retroviral nucleocapsid zinc fingers and inactivates HIV virions

Retrovirology

Volumn 9, Issue , 2012, Pages

  Vercruysse, Thomas ^a   Basta, Beata ^b   Dehaen, Wim ^c   Humbert, Nicolas ^b   Balzarini, Jan ^a   Debaene, François ^b,d   Sanglier Cianférani, Sarah ^b,d   Pannecouque, Christophe ^a   Mély, Yves ^b   Daelemans, Dirk ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c UNIVERSITY OF LEUVEN   (Belgium)

^d CNRS   (France)

Author keywords

HIV; Microbicide; Nucleocapsid; Virucide

Indexed keywords

2 METHYL 3 PHENYL 2H [1,2,4]THIADIAZOL 5 YLIDENEAMINE; ANTIRETROVIRUS AGENT; GAG PROTEIN; GENOMIC RNA; NUCLEOCAPSID PROTEIN; NUCLEOCAPSID PROTEIN 7; OLIGONUCLEOTIDE; UNCLASSIFIED DRUG; WDO 217; ZINC;

ANTIVIRAL ACTIVITY; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG EFFECT; DRUG EXPOSURE; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; MOLECULAR WEIGHT; NONHUMAN; PROTEIN BINDING; REAL TIME POLYMERASE CHAIN REACTION; VIRION; VIRUS CELL INTERACTION; VIRUS INACTIVATION; VIRUS INFECTIVITY; VIRUS ISOLATION; VIRUS PARTICLE; VIRUS TRANSMISSION; WILD TYPE;

ANTI-HIV AGENTS; CD4-POSITIVE T-LYMPHOCYTES; CELL LINE; HIV INFECTIONS; HIV-1; HIV-2; HUMANS; NUCLEOCAPSID; THIADIAZOLES; VIRION; VIRUS INACTIVATION; ZINC; ZINC FINGERS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 84868657764     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-9-95     Document Type: Article

References (54)

1. Mayer KH, Peipert J, Fleming T, Fullem A, Moench T, Cu-Uvin S, Bentley M, Chesney M, Rosenberg Z. Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. Clin Infect Dis 2001, 32:476-482. 10.1086/318496, 11170957.
2. Andrei G, Lisco A, Vanpouille C, Introini A, Balestra E, van den Oord J, Cihlar T, Perno CF, Snoeck R, Margolis L, Balzarini J. Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication. Cell Host Microbe 2011, 10:379-389. 10.1016/j.chom.2011.08.015, 3201796, 22018238.
3. Thomas JA, Gorelick RJ. Nucleocapsid protein function in early infection processes. Virus Res 2008, 134:39-63. 10.1016/j.virusres.2007.12.006, 2789563, 18279991.
4. Krishnamoorthy G, Roques B, Darlix JL, Mely Y. DNA condensation by the nucleocapsid protein of HIV-1: a mechanism ensuring DNA protection. Nucleic Acids Res 2003, 31:5425-5432. 10.1093/nar/gkg738, 203321, 12954779.
5. Lapadat-Tapolsky M, De Rocquigny H, Van Gent D, Roques B, Plasterk R, Darlix JL. Interactions between HIV-1 nucleocapsid protein and viral DNA may have important functions in the viral life cycle. Nucleic Acids Res 1993, 21:831-839. 10.1093/nar/21.4.831, 309214, 8383840.
6. Tanchou V, Gabus C, Rogemond V, Darlix JL. Formation of stable and functional HIV-1 nucleoprotein complexes in vitro. J Mol Biol 1995, 252:563-571. 10.1006/jmbi.1995.0520, 7563074.
7. Rice WG, Schaeffer CA, Graham L, Bu M, McDougal JS, Orloff SL, Villinger F, Young M, Oroszlan S, Fesen MR, et al. The site of antiviral action of 3-nitrosobenzamide on the infectivity process of human immunodeficiency virus in human lymphocytes. Proc Natl Acad Sci U S A 1993, 90:9721-9724. 10.1073/pnas.90.20.9721, 47642, 7692451.
8. Rice WG, Supko JG, Malspeis L, Buckheit RW, Clanton D, Bu M, Graham L, Schaeffer CA, Turpin JA, Domagala J, et al. Inhibitors of HIV nucleocapsid protein zinc fingers as candidates for the treatment of AIDS. Science 1995, 270:1194-1197. 10.1126/science.270.5239.1194, 7502043.
9. Witvrouw M, Balzarini J, Pannecouque C, Jhaumeer-Laulloo S, Este JA, Schols D, Cherepanov P, Schmit JC, Debyser Z, Vandamme AM, et al. SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus. Antimicrob Agents Chemother 1997, 41:262-268. 163699, 9021177.
10. Rice WG, Baker DC, Schaeffer CA, Graham L, Bu M, Terpening S, Clanton D, Schultz R, Bader JP, Buckheit RW, et al. Inhibition of multiple phases of human immunodeficiency virus type 1 replication by a dithiane compound that attacks the conserved zinc fingers of retroviral nucleocapsid proteins. Antimicrob Agents Chemother 1997, 41:419-426. 163723, 9021201.
11. Rice WG, Turpin JA, Huang M, Clanton D, Buckheit RW, Covell DG, Wallqvist A, McDonnell NB, DeGuzman RN, Summers MF, et al. Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein. Nat Med 1997, 3:341-345. 10.1038/nm0397-341, 9055865.
12. Goebel FD, Hemmer R, Schmit JC, Bogner JR, de Clercq E, Witvrouw M, Pannecouque C, Valeyev R, Vandevelde M, Margery H, Tassignon JP. Phase I/II dose escalation and randomized withdrawal study with add-on azodicarbonamide in patients failing on current antiretroviral therapy. AIDS 2001, 15:33-45. 10.1097/00002030-200101050-00007, 11192866.
13. Turpin JA, Song Y, Inman JK, Huang M, Wallqvist A, Maynard A, Covell DG, Rice WG, Appella E. Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers. J Med Chem 1999, 42:67-86. 10.1021/jm9802517, 9888834.
14. Pannecouque C, Szafarowicz B, Volkova N, Bakulev V, Dehaen W, Mely Y, Daelemans D. Inhibition of HIV-1 replication by a bis-thiadiazolbenzene-1,2-diamine that chelates zinc ions from retroviral nucleocapsid zinc fingers. Antimicrob Agents Chemother 2010, 54:1461-1468. 10.1128/AAC.01671-09, 2849360, 20124006.
15. Jenkins LM, Byrd JC, Hara T, Srivastava P, Mazur SJ, Stahl SJ, Inman JK, Appella E, Omichinski JG, Legault P. Studies on the mechanism of inactivation of the HIV-1 nucleocapsid protein NCp7 with 2-mercaptobenzamide thioesters. J Med Chem 2005, 48:2847-2858. 10.1021/jm0492195, 15828823.
16. Turpin JA, Schito ML, Jenkins LM, Inman JK, Appella E. Topical microbicides: a promising approach for controlling the AIDS pandemic via retroviral zinc finger inhibitors. Adv Pharmacol 2008, 56:229-256.
17. Wallace GS, Cheng-Mayer C, Schito ML, Fletcher P, Miller Jenkins LM, Hayashi R, Neurath AR, Appella E, Shattock RJ. Human immunodeficiency virus type 1 nucleocapsid inhibitors impede trans infection in cellular and explant models and protect nonhuman primates from infection. J Virol 2009, 83:9175-9182. 10.1128/JVI.00820-09, 2738238, 19587055.
18. Pannecouque C, Daelemans D, De Clercq E. Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later. Nat Protoc 2008, 3:427-434. 10.1038/nprot.2007.517, 18323814.
19. Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, Desmyter J, De Clercq E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods 1988, 20:309-321. 10.1016/0166-0934(88)90134-6, 2460479.
20. Jordan A, Defechereux P, Verdin E. The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J 2001, 20:1726-1738. 10.1093/emboj/20.7.1726, 145503, 11285236.
21. Yarchoan R, Klecker RW, Weinhold KJ, Markham PD, Lyerly HK, Durack DT, Gelmann E, Lehrman SN, Blum RM, Barry DW, et al. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet 1986, 1:575-580.
22. Bertaux C, Daelemans D, Meertens L, Cormier EG, Reinus JF, Peumans WJ, Van Damme EJ, Igarashi Y, Oki T, Schols D, et al. Entry of hepatitis C virus and human immunodeficiency virus is selectively inhibited by carbohydrate-binding agents but not by polyanions. Virology 2007, 366:40-50. 10.1016/j.virol.2007.04.008, 17498767.
23. Bombarda E, Grell E, Roques BP, Mely Y. Molecular mechanism of the Zn2 + -induced folding of the distal CCHC finger motif of the HIV-1 nucleocapsid protein. Biophys J 2007, 93:208-217. 10.1529/biophysj.106.101378, 1914429, 17416621.
24. Mely Y, De Rocquigny H, Morellet N, Roques BP, Gerad D. Zinc binding to the HIV-1 nucleocapsid protein: a thermodynamic investigation by fluorescence spectroscopy. Biochemistry 1996, 35:5175-5182. 10.1021/bi952587d, 8611501.
25. Loo JA, Holler TP, Sanchez J, Gogliotti R, Maloney L, Reily MD. Biophysical characterization of zinc ejection from HIV nucleocapsid protein by anti-HIV 2,2-dithiobis[benzamides] and benzisothiazolones. J Med Chem 1996, 39:4313-4320. 10.1021/jm960253w, 8863808.
26. Azoulay J, Clamme JP, Darlix JL, Roques BP, Mely Y. Destabilization of the HIV-1 complementary sequence of TAR by the nucleocapsid protein through activation of conformational fluctuations. J Mol Biol 2003, 326:691-700. 10.1016/S0022-2836(02)01430-4, 12581633.
27. Beltz H, Azoulay J, Bernacchi S, Clamme JP, Ficheux D, Roques B, Darlix JL, Mely Y. Impact of the terminal bulges of HIV-1 cTAR DNA on its stability and the destabilizing activity of the nucleocapsid protein NCp7. J Mol Biol 2003, 328:95-108. 10.1016/S0022-2836(03)00244-4, 12684000.
28. Bernacchi S, Stoylov S, Piemont E, Ficheux D, Roques BP, Darlix JL, Mely Y. HIV-1 nucleocapsid protein activates transient melting of least stable parts of the secondary structure of TAR and its complementary sequence. J Mol Biol 2002, 317:385-399. 10.1006/jmbi.2002.5429, 11922672.
29. Beltz H, Clauss C, Piemont E, Ficheux D, Gorelick RJ, Roques B, Gabus C, Darlix JL, de Rocquigny H, Mely Y. Structural determinants of HIV-1 nucleocapsid protein for cTAR DNA binding and destabilization, and correlation with inhibition of self-primed DNA synthesis. J Mol Biol 2005, 348:1113-1126. 10.1016/j.jmb.2005.02.042, 15854648.
30. Bernacchi S, Mely Y. Exciton interaction in molecular beacons: a sensitive sensor for short range modifications of the nucleic acid structure. Nucleic Acids Res 2001, 29:E62. 10.1093/nar/29.13.e62, 55786, 11433038.
31. Shvadchak VV, Klymchenko AS, de Rocquigny H, Mely Y. Sensing peptide-oligonucleotide interactions by a two-color fluorescence label: application to the HIV-1 nucleocapsid protein. Nucleic Acids Res 2009, 37:e25. 10.1093/nar/gkn1083, 2647317, 19151084.
32. Bourbigot S, Ramalanjaona N, Boudier C, Salgado GF, Roques BP, Mely Y, Bouaziz S, Morellet N. How the HIV-1 nucleocapsid protein binds and destabilises the (-)primer binding site during reverse transcription. J Mol Biol 2008, 383:1112-1128. 10.1016/j.jmb.2008.08.046, 18773912.
33. De Guzman RN, Wu ZR, Stalling CC, Pappalardo L, Borer PN, Summers MF. Structure of the HIV-1 nucleocapsid protein bound to the SL3 psi-RNA recognition element. Science 1998, 279:384-388. 10.1126/science.279.5349.384, 9430589.
34. Mahmood N, Jhaumeer-Lauloo S, Sampson J, Houghton PJ. Anti-HIV activity and mechanism of action of macrocyclic diamide SRR-SB3. J Pharm Pharmacol 1998, 50:1339-1342.
35. Miller Jenkins LM, Ott DE, Hayashi R, Coren LV, Wang D, Xu Q, Schito ML, Inman JK, Appella DH, Appella E. Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer. Nat Chem Biol 2010, 6:887-889. 10.1038/nchembio.456, 2997617, 20953192.
36. Darlix JL, Godet J, Ivanyi-Nagy R, Fosse P, Mauffret O, Mely Y. Flexible Nature and Specific Functions of the HIV-1 Nucleocapsid Protein. J Mol Biol 2011, 410:565-581. 10.1016/j.jmb.2011.03.037, 21762801.
37. Godet J, Boudier C, Humbert N, Ivanyi-Nagy R, Darlix JL, Mely Y. Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1. Virus Res 2012, In press.
38. Rice WG, Schaeffer CA, Harten B, Villinger F, South TL, Summers MF, Henderson LE, Bess JW, Arthur LO, McDougal JS, et al. Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds. Nature 1993, 361:473-475. 10.1038/361473a0, 8429889.
39. Schito ML, Soloff AC, Slovitz D, Trichel A, Inman JK, Appella E, Turpin JA, Barratt-Boyes SM. Preclinical evaluation of a zinc finger inhibitor targeting lentivirus nucleocapsid protein in SIV-infected monkeys. Curr HIV Res 2006, 4:379-386. 10.2174/157016206777709492, 16842089.
40. Urbaneja MA, Kane BP, Johnson DG, Gorelick RJ, Henderson LE, Casas-Finet JR. Binding properties of the human immunodeficiency virus type 1 nucleocapsid protein p7 to a model RNA: elucidation of the structural determinants for function. J Mol Biol 1999, 287:59-75. 10.1006/jmbi.1998.2521, 10074407.
41. Vuilleumier C, Bombarda E, Morellet N, Gerard D, Roques BP, Mely Y. Nucleic acid sequence discrimination by the HIV-1 nucleocapsid protein NCp7: a fluorescence study. Biochemistry 1999, 38:16816-16825. 10.1021/bi991145p, 10606514.
42. Amarasinghe GK, De Guzman RN, Turner RB, Chancellor KJ, Wu ZR, Summers MF. NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi-RNA packaging signal. Implications for genome recognition. J Mol Biol 2000, 301:491-511. 10.1006/jmbi.2000.3979, 10926523.
43. Bazzi A, Zargarian L, Chaminade F, Boudier C, De Rocquigny H, Rene B, Mely Y, Fosse P, Mauffret O. Structural insights into the cTAR DNA recognition by the HIV-1 nucleocapsid protein: role of sugar deoxyriboses in the binding polarity of NC. Nucleic Acids Res 2011, 39:3903-3916. 10.1093/nar/gkq1290, 3089453, 21227929.
44. Morellet N, Demene H, Teilleux V, Huynh-Dinh T, de Rocquigny H, Fournie-Zaluski MC, Roques BP. Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the single-stranded pentanucleotide d(ACGCC). J Mol Biol 1998, 283:419-434. 10.1006/jmbi.1998.2098, 9769215.
45. Avilov SV, Piemont E, Shvadchak V, de Rocquigny H, Mely Y. Probing dynamics of HIV-1 nucleocapsid protein/target hexanucleotide complexes by 2-aminopurine. Nucleic Acids Res 2008, 36:885-896. 2241888, 18086707.
46. Godet J, Ramalanjaona N, Sharma KK, Richert L, de Rocquigny H, Darlix JL, Duportail G, Mely Y. Specific implications of the HIV-1 nucleocapsid zinc fingers in the annealing of the primer binding site complementary sequences during the obligatory plus strand transfer. Nucleic Acids Res 2011, 39:6633-6645. 10.1093/nar/gkr274, 3159456, 21543454.
47. Rossio JL, Esser MT, Suryanarayana K, Schneider DK, Bess JW, Vasquez GM, Wiltrout TA, Chertova E, Grimes MK, Sattentau Q, et al. Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol 1998, 72:7992-8001. 110135, 9733838.
48. Altfeld M, Fadda L, Frleta D, Bhardwaj N. DCs and NK cells: critical effectors in the immune response to HIV-1. Nat Rev Immunol 2011, 11:176-186. 10.1038/nri2935, 3278081, 21350578.
49. van der Vlist M, van der Aar AM, Gringhuis SI, Geijtenbeek TB. Innate signaling in HIV-1 infection of dendritic cells. Curr Opin HIV AIDS 2011, 6:348-352. 10.1097/COH.0b013e328349a2d1, 21743322.
50. Jordan A, Bisgrove D, Verdin E. HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J 2003, 22:1868-1877. 10.1093/emboj/cdg188, 154479, 12682019.
51. Daelemans D, De Clercq E, Vandamme AM. A quantitative GFP-based bioassay for the detection of HIV-1 Tat transactivation inhibitors. J Virol Methods 2001, 96:183-188. 10.1016/S0166-0934(01)00330-5, 11445148.
52. Daelemans D, Pannecouque C, Pavlakis GN, Tabarrini O, De Clercq E. A novel and efficient approach to discriminate between pre- and post-transcription HIV inhibitors. Mol Pharmacol 2005, 67:1574-1580. 10.1124/mol.104.010249, 15728798.
53. Daelemans D, Pauwels R, De Clercq E, Pannecouque C. A time-of-drug addition approach to target identification of antiviral compounds. Nat Protoc 2011, 6:925-933. 10.1038/nprot.2011.330, 21637207.
54. Vercruysse T, Pardon E, Vanstreels E, Steyaert J, Daelemans D. An intrabody based on a llama single-domain antibody targeting the N-terminal alpha-helical multimerization domain of HIV-1 rev prevents viral production. J Biol Chem 2010, 285:21768-21780. 10.1074/jbc.M110.112490, 2898381, 20406803.