GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 Variants in Vitro

Antimicrobial Agents and Chemotherapy

Volumn 57, Issue 5, 2013, Pages 2036-2046

  Amano, Masayuki ^a   Tojo, Yasushi ^a   Salcedo Gómez, Pedro Miguel ^a   Campbell, Joseph Richard ^a   Das, Debananda ^d   Aoki, Manabu ^a,b   Xu, Chun Xiao ^c   Rao, Kalapala Venkateswara ^c   Ghosh, Arun K ^c   Mitsuya, Hiroaki ^a,d  

^a KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^b KUMAMOTO HEALTH SCIENCE UNIVERSITY   (Japan)

^c PURDUE UNIVERSITY   (United States)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; ATAZANAVIR; DARUNAVIR; GRL 0519; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; LOPINAVIR; RITONAVIR; SAQUINAVIR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG POTENCY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; IN VITRO STUDY; LONG TERM CARE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; VIRUS INFECTIVITY; VIRUS ISOLATION; VIRUS REPLICATION; VIRUS STRAIN;

AMINO ACID SEQUENCE; BINDING SITES; CARBAMATES; CELL LINE, TUMOR; DRUG RESISTANCE, VIRAL; FURANS; HIV PROTEASE; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; INHIBITORY CONCENTRATION 50; LOPINAVIR; MOLECULAR DOCKING SIMULATION; MOLECULAR SEQUENCE DATA; OLIGOPEPTIDES; PROTEIN BINDING; PYRIDINES; RITONAVIR; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; T-LYMPHOCYTES; VIRUS REPLICATION;

EID: 84876207904     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.02189-12     Document Type: Article

References (38)

1. Edmonds A, Yotebieng M, Lusiama J, Matumona Y, Kitetele F, Napravnik S, Cole SR, Van Rie A, Behets F. 2011. The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study. PLoS Med. 8:e1001044. doi:10 .1371/journal.pmed.1001044.
2. Lohse N, Hansen AB, Gerstoft J, Obel N. 2007. Improved survival in HIV-infected persons: consequences and perspectives. J. Antimicrob. Chemother. 60:461-463.
3. Mitsuya H, Maeda K, Das D, Ghosh AK. 2008. Development of protease inhibitors and the fight with drug-resistant HIV-1 variants. Adv. Pharmacol. 56:169-197.
4. Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, Weinstein MC, Freedberg KA. 2006. The survival benefits of AIDS treatment in the United States. J. Infect. Dis. 194:11-19.
5. De Clercq E. 2002. Strategies in the design of antiviral drugs. Nat. Rev. Drug Discov. 1:13-25.
6. Siliciano JD, Siliciano RF. 2004. A long-term latent reservoir for HIV-1. J. Antimicrob. Chemother. 54:6-9.
7. Simon V, Ho DD. 2003. HIV-1 dynamics in vivo: implications for therapy. Nat. Rev. Microbiol. 1:181-190.
8. Carr A. 2003. Toxicity of antiretroviral therapy and implications for drug development. Nat. Rev. Drug Discov. 2:624-634.
9. Fumero E, Podzamczer D. 2003. New patterns of HIV-1 resistance during HAART. Clin. Microbiol. Infect. 9:1077-1084.
10. Grabar S, Weiss L, Costagliola D. 2006. HIV infection in older patients in the HAART era. J. Antimicrob. Chemother. 57:4-7.
11. Hirsch HH, Kaufmann G, Sendi P, Battegay M. 2004. Immune reconstitution in HIV-infected patients. Clin. Infect. Dis. 38:1159-1166.
12. Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, Koup RA, Mellors JW, Connick E, Conway B, Kilby M, Wang L, Whitcomb JM, Hellmann NS, Richman DD. 2002. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 347:385-394.
13. Naggie S, Hicks C. 2010. Protease inhibitor-based antiretroviral therapy in treatment-naive HIV-1-infected patients: the evidence behind the options. J. Antimicrob. Chemother. 65:1094-1099.
14. Ghosh AK, Kincaid JF, Cho W, Walters DE, Krishnan K, Hussain KA, Koo Y, Cho H, Rudall C, Holland L, Buthod J. 1998. Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)- (hydroxyethylamino)sulfonamide isostere. Bioorg. Med. Chem. Lett. 8:687-690.
15. Ghosh AK, Krishnan K, Walters DE, Cho W, Cho H, Koo Y, Trevino J, Holland L, Buthod J. 1998. Structure based design: novel spirocyclic ethers as nonpeptidal P2-ligands for HIV protease inhibitors. Bioorg. Med. Chem. Lett. 8:979-982.
16. Koh Y, Nakata H, Maeda K, Ogata H, Bilcer G, Devasamudram T, Kincaid JF, Boross P, Wang YF, Tie Y, Volarath P, Gaddis L, Harrison RW, Weber IT, Ghosh AK, Mitsuya H. 2003. Novel bistetrahydrofuranylurethane- containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 47:3123-3129.
17. Ghosh AK, Xu CX, Rao KV, Baldridge A, Agniswamy J, Wang YF, Weber IT, Aoki M, Miguel SG, Amano M, Mitsuya H. 2010. Probing multidrug-resistance and protein-ligand interactions with oxatricyclic designed ligands in HIV-1 protease inhibitors. ChemMedChem 5:1850-1854.
18. Shirasaka T, Kavlick MF, Ueno T, Gao WY, Kojima E, Alcaide ML, Chokekijchai S, Roy BM, Arnold E, Yarchoan R, Mitsuya H. 1995. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. U. S. A. 92:2398-2402.
19. Yoshimura K, Kato R, Kavlick MF, Nguyen A, Maroun V, Maeda K, Hussain KA, Ghosh AK, Gulnik SV, Erickson JW, Mitsuya H. 2002. A potent human immunodeficiency virus type 1 protease inhibitor, UIC- 94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. J. Virol. 76:1349-1358.
20. Yoshimura K, Kato R, Yusa K, Kavlick MF, Maroun V, Nguyen A, Mimoto T, Ueno T, Shintani M, Falloon J, Masur H, Hayashi H, Erickson J, Mitsuya H. 1999. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proc. Natl. Acad. Sci. U. S. A. 96:8675-8680.
21. Ghosh AK, Leshchenko S, Noetzel M. 2004. Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone: synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UIC-94017 (TMC-114). J. Org. Chem. 69:7822-7829.
22. Maeda K, Yoshimura K, Shibayama S, Habashita H, Tada H, Sagawa K, Miyakawa T, Aoki M, Fukushima D, Mitsuya H. 2001. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. 276:35194-35200.
23. Nakata H, Amano M, Koh Y, Kodama E, Yang G, Bailey CM, Kohgo S, Hayakawa H, Matsuoka M, Anderson KS, Cheng YC, Mitsuya H. 2007. Activity against human immunodeficiency virus type 1, intracellular metabolism, and effects on humanDNApolymerases of 4=-ethynyl-2-fluoro- 2=-deoxyadenosine. Antimicrob. Agents Chemother. 51:2701-2708.
24. Amano M, Koh Y, Das D, Li J, Leschenko S, Wang YF, Boross PI, Weber IT, Ghosh AK, Mitsuya H. 2007. A novel bistetrahydrofuranylurethane- containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 51: 2143-2155.
25. Ide K, Aoki M, Amano M, Koh Y, Yedidi RS, Das D, Leschenko S, Chapsal B, Ghosh AK, Mitsuya H. 2011. Novel HIV-1 protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyranotetrahydrofuran, that are potent against multi-PI-resistant HIV-1 variants. Antimicrob. Agents Chemother. 55:1717-1727.
26. Tojo Y, Koh Y, Amano M, Aoki M, Das D, Kulkarni S, Anderson DD, Ghosh AK, Mitsuya H. 2010. Novel protease inhibitors (PIs) containing macrocyclic components and 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro. Antimicrob. Agents Chemother. 54:3460-3470.
27. Kaminski GA, Friesner EA. 2001. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B 105:6474-6487.
28. Koh Y, Amano M, Towata T, Danish M, Leshchenko-Yashchuk S, Das D, Nakayama M, Tojo Y, Ghosh AK, Mitsuya H. 2010. In vitro selection of highly darunavir-resistant and replication-competent HIV-1 variants by using a mixture of clinical HIV-1 isolates resistant to multiple conventional protease inhibitors. J. Virol. 84:11961-11969.
29. Schon A, Ingaramo M, Freire E. 2003. The binding of HIV-1 protease inhibitors to human serum proteins. Biophys. Chem. 105:221-230.
30. Marcelin AG, Affolabi D, Lamotte C, Mohand HA, Delaugerre C, Wirden M, Voujon D, Bossi P, Ktorza N, Bricaire F, Costagliola D, Katlama C, Peytavin G, Calvez V. 2004. Resistance profiles observed in virological failures after 24 weeks of amprenavir/ritonavir containing regimen in protease inhibitor experienced patients. J. Med. Virol. 74:16-20.
31. Young TP, Parkin NT, Stawiski E, Pilot-Matias T, Trinh R, Kempf DJ, Norton M. 2010. Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Antimicrob. Agents Chemother. 54:4903-4906.
32. Aoki M, Danish ML, Aoki-Ogata H, Amano M, Ide K, Koh Y, Mitsuya H. 2012. The loss of protease dimerization inhibition activity of tipranavir (TPV) and its association with HIV-1 acquisition of resistance to TPV. J. Virol. 86:13384-13396.
33. Wlodawer A, Vondrasek J. 1998. Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annu. Rev. Biophys. Biomol. Struct. 27:249-284.
34. Wlodawer A, Erickson JW. 1993. Structure-based inhibitors of HIV-1 protease. Annu. Rev. Biochem. 62:543-585.
35. Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Leschenko S, Baldridge A, Shioda T, Yarchoan R, Ghosh AK, Mitsuya H. 2007. Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J. Biol. Chem. 282:28709-28720.
36. Dunn BM, Goodenow MM, Gustchina A, Wlodawer A. 2002. Retroviral proteases. Genome Biol. 3:reviews3006.1-reviews3006.7. doi:10.1186/gb -2002-3-4-reviews3006.
37. Fournier T, Medjoubi NN, Porquet D. 2000. Alpha-1-acid glycoprotein. Biochim. Biophys. Acta 1482:157-171.
38. Boffito M, Miralles D, Hill A. 2008. Pharmacokinetics, efficacy, and safety of darunavir/ritonavir 800/100 mg once-daily in treatment-naïve and -experienced patients. HIV Clin. Trials 9:418-427.