The novel cyclophilin inhibitor CPI-431-32 concurrently blocks HCV and HIV-1 infections via a similar mechanism of action

PLoS ONE

Volumn 10, Issue 8, 2015, Pages

  Gallay, Philippe A ^a   Bobardt, Michael D ^a   Chatterji, Udayan ^a   Trepanier, Daniel J ^b   Ure, Daren ^b   Ordonez, Cosme ^b   Foster, Robert ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b Ciclofilin Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALISPORIVIR; CPI 431 32; CYCLOPHILIN A; CYCLOSPORIN A DERIVATIVE; DACLATASVIR; NELFINAVIR; UNCLASSIFIED DRUG; ANTIVIRUS AGENT; CAPSID PROTEIN; CYCLOPHILIN; CYCLOSPORIN DERIVATIVE; PROTEIN BINDING;

ANTIVIRAL RESISTANCE; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; CORRELATIONAL STUDY; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; GENOME; HEPATITIS C; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VITRO STUDY; MIXED INFECTION; PROTEIN INTERACTION; REVERSE TRANSCRIPTION; VIRUS CAPSID; VIRUS REPLICATION; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CELL LINE; COCULTURE; DRUG EFFECTS; HEPACIVIRUS; HIV INFECTIONS; METABOLISM; VIROLOGY;

ANTIVIRAL AGENTS; CAPSID PROTEINS; CELL LINE; CELLS, CULTURED; COCULTURE TECHNIQUES; COINFECTION; CYCLOPHILINS; CYCLOSPORINS; DRUG RESISTANCE, VIRAL; HEPACIVIRUS; HEPATITIS C; HIV INFECTIONS; HIV-1; HUMANS; PROTEIN BINDING; REVERSE TRANSCRIPTION; VIRUS REPLICATION;

EID: 84942924101     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0134707     Document Type: Article

References (77)

1. Operskalski EA, Kovacs A (2011) HIV/HCV co-infection: pathogenesis, clinical complications, treatment, and new therapeutic technologies. Curr HIV/AIDS Rep 8:12-22. doi: 10.1007/s11904-010-0071-3 PMID: 21221855
2. Coste J, Reesink HW, Engelfriet CP, Laperche S, Brown S, Busch MP, et al. (2005) Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003. Vox Sang 88:289-303. PMID: 15877653
3. Sulkowski MS, Thomas DL (2003) Hepatitis C in the HIV-Infected Person. Ann Intern Med 138:197-207. PMID: 12558359
4. Garfein RS, Vlahov D, Galai N, Doherty MC, Nelson KE (1996) Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses. Am J Public Health 86:655-661. PMID: 8629715
5. Garten RJ, Lai S, Zhang J, Liu W, Chen J, Vlahov D, et al. (2004) Rapid transmission of hepatitis C virus among young injecting heroin users in Southern China. Int J Epidemiol 33:182-188. PMID: 15075167
6. Quan VM, Go VF, Namle V, Bergenstrom A, Thuoc NP, Zenilman J, et al. (2009) Risks for HIV, HBV, and HCV infections among male injection drug users in northern Vietnam: a case-control study. AIDS Care 21:7-16. doi: 10.1080/09540120802017610 PMID: 19085215
7. Alter MJ (2006) Epidemiology of viral hepatitis and HIVcoinfection. J Hepatol 44:S6-S9. PMID: 16352363
8. Thomas DL, Vlahov D, Solomon L, Cohn S, Taylor E, Garfein R, et al. (1995) Correlates of hepatitis C virus infections among injection drug users. Medicine (Baltimore) 74:212-220.
9. Villano SA, Vlahov D, Nelson KE, Lyles CM, Cohn S, Thomas DL (1997) Incidence and risk factors for hepatitis C among injection drug users in Baltimore, Maryland. J Clin Microbiol 35:3274-3277. PMID: 9399533
10. Larsen MV, Omland LH, Gerstoft J, Larsen CS, Jensen J, Obel N, et al. (2010) Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population based cohort study. Addiction 105:529-535. doi: 10.1111/j.1360-0443.2009.02827.x PMID: 20402997
11. Hernandez MD, Sherman KE (2011) HIV/hepatitis Ccoinfection natural history and disease progression. CurrOpin HIV AIDS 6:478-82. doi: 10.1097/COH.0b013e32834bd365 PMID: 22001892
12. Kim AY, Chung RT (2009) Coinfection with HIV-1 and HCV-a one-two punch. Gastroenterology 137:795-814. doi: 10.1053/j.gastro.2009.06.040 PMID: 19549523
13. Sherman KE (2004) HCV and HIV: atale of two viruses. Rev Gastroenterol Disord 4 Suppl 1:S48-54. \ Review. PMID: 15185718
14. López-Diéguez M, Montes ML, Pascual-Pareja JF, Quereda C, Von Wichmann MA, Berenguer J, et al. (2011) The natural history of liver cirrhosis in HIV-hepatitisCvirus-coinfected patients. AIDS 25:899-904. doi: 10.1097/QAD.0b013e3283454174 PMID: 21330908
15. Loko MA, Salmon D, Carrieri P, Winnock M, Mora M, Merchadou L, et al. (2010) The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): early findings, 2006-2010. BMC Infect Dis 10:303-313. doi: 10.1186/1471-2334-10-303 PMID: 20969743
16. Thein HH, Yi Q, Dore GJ, Krahn MD (2008) Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 22:1979-91. doi: 10.1097/QAD.0b013e32830e6d51 PMID: 18784461
17. Tuyama AC, Hong F, Saiman Y, Wang C, Ozkok D, Mosoian A, et al. (2010) Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattrac-tant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis. Hepatology 52:612-22. doi: 10.1002/hep. 23679 PMID: 20683959
18. Smit C, Van Den Berg C, Geskus R, Berkhout B, Coutinho R, Prins M (2008) Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study. J Acquir Immune Defic Syndr 47:221-5. doi: 10. 1097/QAI.0b013e31815d2f59 PMID: 18223361
19. Al-Harthi L, Voris J, Du W, Wright D, Nowicki M, Frederick T, et al. (2006) Evaluating the impact of hepatitis C virus (HCV) on highly active antiretroviral therapy-mediated immune responses in HCV/HIV-coinfected women: role of HCV on expression of primed/memory T cells. J Infect Dis 193:1202-10. PMID: 16586355
20. Franke EK, Yuan HE, Luban J (1994) Specific incorporation of cyclophilin A into HIV-1 virions. Nature 372:359-362. PMID: 7969494
21. Thali M, Bukovsky A, Kondo E, Rosenwirth B, Walsh CT, Sodroski J, et al. (1994) Functional association of cyclophilin A with HIV-1 virions. Nature 372:363-365. PMID: 7969495
22. Rosenwirth B, Billich A, Datema R, Donatsch P, Hammerschmid F, Harrison R, et al. (1994) Inhibition of human immunodeficiency virus type 1 replication by SDZNIM811, anonimmunosuppressivecyclo-sporine analog. Antimicrob Agents Chemother 38:1763-1772. PMID: 7527198
23. Towers GJ, Hatziioannou T, Cowan S, Goff SP, Luban J, Bieniasz PD (2003) Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nat Med 9:1138-1143. PMID: 12897779
24. Hilditch L, Towers GJ (2014) A model for cofactor use during HIV-1 reverse transcription and nuclear entry. CurrOpin Virol 4:32-36. doi: 10.1016/j.coviro.2013.11.003 PMID: 24525292
25. Hopkins S, Gallay PA (2014) The role of immunophilins in viral infection. BiochimBiophysActa pii: S0304-4165 (14) 00388-2. doi: 10.1016/j.bbagen. 2014.11.011
26. Watashi K, Hijikata M, Hosaka M, Yamaji M, Shimotohno K (2003) Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 38:1282-1288. PMID: 14578868
27. Nakagawa M, Sakamoto N, Tanabe Y, Koyama T, Itsui Y, Takeda Y, et al. (2005) Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins. Gastroenterology 129:1031-1041. PMID: 16143140
28. Ma S, Boerner JE, Tiong Yip C, Weidmann B, Ryder NS, Cooreman MP, et al. (2006) NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon. Antimicrob Agents Chemother 50:2976-2982. PMID: 16940091
29. Ishii N, Watashi K, Hishiki T, Goto K, Inoue D, Hijikata M, et al. (2006) Diverse effects of cyclosporine on hepatitis C virus strain replication. J Virol 80:4510-4520. PMID: 16611911
30. Goto K, Watashi K, Murata T, Hishiki T, Hijikata M, Shimotohno K (2006) Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors, cyclosporin A, and NIM811. Biochem Biophys Res Commun 343:879-884. PMID: 16564500
31. Paeshuyse J, Kaul A, De Clercq E, Rosenwirth B, Dumont JM, Scalfaro P, et al. (2006) The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro. Hepatology 43:761-770. PMID: 16557546
32. Yang F, Robotham JM, Nelson HB, Irsigler A, Kenworthy R, Tang H (2008) Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol 82:5269-5278. doi: 10.1128/JVI.02614-07 PMID: 18385230
33. Flisiak R, Horban A, Gallay P, Bobardt M, Selvarajah S, Wiercinska-Drapalo A, et al. (2008) The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology 47:817-26. doi: 10.1002/hep. 22131 PMID: 18302285
34. Flisiak R, Feinman SV, Jablkowski M, Horban A, Kryczka W, Pawlowska M, et al. (2009) The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients. Hepatology 49:1460-8. doi: 10.1002/hep. 22835 PMID: 19353740
35. Kaul A, Stauffer S, Berger C, Pertel T, Schmitt J, Kallis S, et al. (2009) Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein cleavage kinetics. PLoS Pathog 5:e1000546. doi: 10.1371/journal.ppat.1000546 PMID: 19680534
36. Chatterji U, Bobardt M, Selvarajah S, Yang F, Tang H, Sakamoto N, et al. (2009) The isomerase active site of cyclophilin A is critical for hepatitis C virus replication. J Biol Chem 284:16998-7005. doi: 10. 1074/jbc. M109.007625 PMID: 19380579
37. Liu Z, Yang F, Robotham JM, Tang H (2009) Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex. J Virol 83:6554-65. doi: 10.1128/JVI.02550-08 PMID: 19386705
38. Gaither LA, Borawski J, Anderson LJ, Balabanis KA, Devay P, Joberty G, et al. (2010) Multiple cyclophilins involved in different cellular pathways mediate HCV replication. Virology 397:43-55. doi: 10. 1016/j.virol.2009.10.043 PMID: 19932913
39. Tang H (2010) Cyclophilin inhibitors as a novel HCV therapy. Viruses 2:1621-34. doi: 10.3390/v2081621 PMID: 21994697
40. Hopkins S, Di Massimo B, Rusnak P, Heuman D, Lalezari J, Sluder A, et al. (2012) The cyclophilin inhibitor SCY-635 suppresses viral replication and induces endogenous interferons in patients with chronic HCV genotype 1 infection. J Hepatol 57:47-54. doi: 10.1016/j.jhep. 2012.02.024 PMID: 22425702
41. Dorner M, Horwitz JA, Donovan BM, Labitt RN, Budell WC, Friling T, et al. (2013) Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 501:237-41. doi: 10.1038/nature12427 PMID: 23903655
42. Naoumov NV (2014) Cyclophilin inhibition as potential therapy for liver diseases. J Hepatol 61:1166-74. doi: 10.1016/j.jhep. 2014.07.008 PMID: 25048953
43. Sweeney ZK, Fu J, Wiedmann B (2014) From chemical tools to clinical medicines: nonimmunosuppres-sive cyclophilin inhibitors derived from the cyclosporin and sanglifehrin scaffolds. J Med Chem 57:7145-59. doi: 10.1021/jm500223x PMID: 24831536
44. Hansson MJ, Moss SJ, Bobardt M, Chatterji U, Coates N, Garcia-Rivera JA, et al. (2015) Bioengineer-ing and semisynthesis of an optimized cyclophilin inhibitor for treatment of chronic viral infection. Chem Biol 22:285-92. doi: 10.1016/j.chembiol.2014.10.023 PMID: 25619934
45. Bobardt MD, Cheng G, De Witte L, Selvarajah S, Chatterji U, Sanders-Beer BE, et al. (2008) Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus. Proc Natl Acad Sci USA 105:5525-5530. doi: 10.1073/pnas.0801388105 PMID: 18378908
46. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, et al. (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA 102:9294-9299. PMID: 15939869
47. Gawlik K, Baugh J, Chatterji U, Lim PJ, Bobardt MD, Gallay PA (2014) HCV core residues critical for infectivity are also involved in core-NS5A complex formation. PLoSOne 9:e88866. doi: 10.1371/journal.pone.0088866 eCollection 2014. PMID: 24533158
48. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, et al. (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791-796. PMID: 15951748
49. Vrolijk JM, Kaul A, Hansen BE, Lohmann V, Haagmans BL, Schalm SW, et al. (2003) A replicon-based bioassayforthe measurement of interferons in patients with chronic hepatitis CJVirol Methods 110:201-209. PMID: 12798249
50. Koutsoudakis G, Kaul A, Steinmann E, Kallis S, Lohmann V, Pietschmann T, et al. (2006) Characterization of the early steps of hepatitis C virus infection by using luciferase reporter viruses. J Virol 80:5308-5320. PMID: 16699011
51. Richman D, Shih CK, Lowy I, Rose J, Prodanovich P, Goff S, et al. (1991) Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc Natl Acad Sci USA 88:11241-11245. PMID: 1722324
52. Jacobsen H, Yasargil K, Winslow DL, Craig JC, Kröhn A, Duncan IB, et al. (1995) Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology 206:527-534. PMID: 7831807
53. Chatterji U, Bobardt MD, Stanfield R, Ptak RG, Pallansch LA, Ward PA, et al. (2005) Naturally occurring capsid substitutions render HIV-1 cyclophilin A independent in human cells and TRIM-cyclophilin-resis-tant in Owl monkey cells. J Biol Chem 280:40293-40300. PMID: 16199531
54. Chatterji U, Garcia-Rivera JA, Baugh J, Gawlik K, Wong KA, Zhong W, et al. (2014) The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance. Antimicrob Agents Chemother 58:3327-34. doi: 10.1128/AAC.00016-14 PMID: 24687498
55. Chatterji U, Lim P, Bobardt MD, Wieland S, Cordek DG, Vuagniaux G, et al. (2010) HCV resistance to cyclosporin A does not correlate with a resistance of the NS5A-cyclophilin A interaction to cyclophilin inhibitors. J Hepatol 53:50-6. doi: 10.1016/j.jhep. 2010.01.041 PMID: 20451281
56. Fischer G, Bang H, Berger E, Schellenberger A (1984) Conformational specificity of chymotrypsin toward proline-containing substrates. Biochim Biophys Acta 791:87-97. PMID: 6498206
57. Kofron JL, Kuzmic P, Kishore V, Colón-Bonilla E, Rich DH (1991) Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Biochemistry 30:6127-6134. PMID: 2059621
58. Ptak RG, Gallay PA, Jochmans D, Halestrap AP, Ruegg UT, Pallansch LA, et al. (2008) Inhibition of human immunodeficiency virus type 1 replication in human cells by Debio-025, a novel cyclophilin binding agent. Antimicrob Agents Chemother 52:1302-17. doi: 10.1128/AAC.01324-07 PMID: 18212100
59. Hopkins S, Bobardt M, Chatterji U, Garcia-Rivera JA, Lim P, Gallay PA (2012) The cyclophilin inhibitor SCY-635 disrupts hepatitis C virus NS5A-cyclophilin A complexes. Antimicrob Agents Chemother 56:3888-97. doi: 10.1128/AAC.00693-12 PMID: 22585215
60. Chatterji U, Bobardt M, Tai A, Wood M, Gallay PA (2015) Cyclophilin and NS5A Inhibitors, but not other Anti-HCV Agents, Preclude HCV-Mediated Formation of Double Membrane Vesicle Viral Factories. Antimicrob Agents Chemother pii: AAC.04958-14.
61. Tai AW, Salloum S (2011) The roleofthephosphatidylinositol4-kinase PI4KAin hepatitis C virus-induced host membrane rearrangement. PLoS One 6:e26300. doi: 10.1371/journal.pone.0026300 PMID: 22022594
62. Garcia-Rivera JA, Bobardt M, Chatterji U, Hopkins S, Gregory MA, Wilkinson B, et al. (2012) Multiple mutations in hepatitis C virus NS5A domain II are required to confer a significant level of resistance to alisporivir. Antimicrob Agents Chemother 56:5113-5121. doi: 10.1128/AAC.00919-12 PMID: 22802259
63. Yang F, Robotham JM, Grise H, Frausto S, Madan V, Zayas M, et al. (2010) A major determinant of cyclophilin dependence and cyclosporine susceptibility of hepatitis C virus identified by a genetic approach. PLoS Pathog 6:e1001118. doi: 10.1371/journal.ppat.1001118 PMID: 20886100
64. Ansari IU, Striker R (2012) Subtype specific differences in NS5A domain II reveals involvement of proline at position 310 in cyclosporine susceptibility of hepatitis C virus. Viruses 4:3303-3315. PMID: 23342381
65. Grisé H, Frausto S, Logan T, Tang H (2012) A conserved tandem cyclophilin-binding site in hepatitis C virus nonstructural protein 5A regulates Alisporivir susceptibility. J Virol 86:4811-22. doi: 10.1128/JVI. 06641-11 PMID: 22345441
66. Ansari IU, Allen T, Berical A, Stock PG, Barin B, Striker R (2013) Phenotypic analysis of NS5A variant from liver transplant patient with increased cyclosporine susceptibility. Virology 436:268-73. doi: 10. 1016/j.virol.2012.11.018 PMID: 23290631
67. Gosert R, Egger D, Lohmann V, Bartenschlager R, Blum HE, Bienz K, et al. (2003) Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 77:5487-5492. PMID: 12692249
68. Wölk B, Büchele B, Moradpour D, Rice CM (2008) A dynamic view of hepatitis C virus replication complexes. J Virol 82:10519-10531. doi: 10.1128/JVI.00640-08 PMID: 18715913
69. Romero-Brey I, Merz A, Chiramel A, Lee JY, Chlanda P, Haselman U, et al. (2012) Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication. PLoS Pathog 8:e1003056. doi: 10.1371/journal.ppat.1003056 PMID: 23236278
70. Paul D, Hoppe S, Saher G, Krijnse-Locker J, Bartenschlager R (2013) Morphological and biochemical characterization of the membranous hepatitis C virus replication compartment. J Virol 87:10612-10627. doi: 10.1128/JVI.01370-13 PMID: 23885072
71. Madan V, Paul D, Lohmann V, Bartenschlager R (2014) Inhibition of HCV Replication by Cyclophilin Antagonists is Linked to Replication Fitness and Occurs by Inhibition of Membranous Web Formation. Gastroenterology pii: S0016-5085 (14) 00146-2. doi: 10.1053/j.gastro.2014.01.055
72. Berger C, Romero-Brey I, Radujkovic D, Terreux R, Zayas M, Paul D, et al. (2014) Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus-induced membranous replication factories, independent of RNA replication. Gastroenterology 147:1094-1105.e25. doi: 10.1053/j.gastro. 2014.07.019 PMID: 25046163
73. Colgan J, Asmal M, Yu B, Luban J (2005) Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine. J Immunol 174:6030-6038. PMID: 15879096
74. Braaten D, Luban J (2001) Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human Tcells. EMBOJ 20:1300-9. PMID: 11250896
75. Marini B, Kertesz-Farkas A, Ali H, Lucic B, Lisek K, Manganaro L, et al. (2015) Nuclear architecture dictates HIV-1 integration site selection. Nature doi: 10.1038/nature14226
76. Lin K, Gallay P (2013) Curing a viral infection by targeting the host: the example of cyclophilin inhibitors. Antiviral Res 99:68-77. doi: 10.1016/j.antiviral.2013.03.020 PMID: 23578729
77. Baugh JM, Garcia-Rivera JA, Gallay PA (2013) Host-targeting agents in the treatment of hepatitis C: a beginning and an end? Antiviral Res 100:555-61. doi: 10.1016/j.antiviral.2013.09.020 PMID: 24091203