Hydroxylated tropolones inhibit hepatitis B virus replication by blocking viral ribonuclease H activity

Antimicrobial Agents and Chemotherapy

Volumn 59, Issue 2, 2015, Pages 1070-1079

  Lu, Gaofeng ^a,b   Lomonosova, Elena ^b,c   Cheng, Xiaohong ^b   Moran, Eileen A ^b   Meyers, Marvin J ^b   Le Grice, Stuart F J ^d   Thomas, Craig J ^e   Jiang, Jian Kang ^e   Meck, Christine ^f,g   Hirsch, Danielle R ^f,g   D'Erasmo, Michael P ^f,g   Suyabatmaz, Duygu M ^f   Murelli, Ryan P ^f,g   Tavis, John E ^b,c  

^a ZHENGZHOU UNIVERSITY   (China)

^b SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Saint Louis University   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

^e NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^f CITY UNIVERSITY OF NEW YORK   (United States)

^g CITY UNIVERSITY OF NEW YORK   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RIBONUCLEASE H; TROPOLONE;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG HYDROXYLATION; EC50; ENZYME ACTIVITY; ENZYME INHIBITION; HEPATITIS B VIRUS; HEPATITIS B VIRUS GENOTYPE D; HUMAN IMMUNODEFICIENCY VIRUS; NONHUMAN; PRIORITY JOURNAL; RNA CLEAVAGE; VIRUS REPLICATION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; HUMAN; METABOLISM;

HEPATITIS B VIRUS; HUMANS; RIBONUCLEASE H; TROPOLONE; VIRUS REPLICATION;

EID: 84921925555     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.04617-14     Document Type: Article

References (53)

1. Lavanchy D. 2004. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 11:97-107. http://dx.doi.org/10.1046/j.1365-2893.2003.00487.x.
2. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. 2006. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 28:112-125. http://dx.doi.org/10.1093/epirev/mxj009.
3. Ganem D, Prince AM. 2004. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med 350:1118-1129. http://dx.doi .org/10.1056/NEJMra031087.
4. Fattovich G, Pantalena M, Zagni I, Realdi G, Schalm SW, Christensen E, European Concerted Action on Viral Hepatitis (EUROHEP). 2002. Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol 97:2886-2895. http://dx.doi.org/10.1111/j.1572-0241.2002.07057.x.
5. Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, McHugh JA, Petersen GM, Rein MF, Strader DB, Trotter HT. 2009. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med 150:104-110. http://dx.doi.org/10.7326/0003-4819-150-2-200901200-00100.
6. Lok AS, McMahon BJ. 2009. Chronic hepatitis B: update 2009. Hepatology 50:661-662. http://dx.doi.org/10.1002/hep.23190.
7. Grimm D, Thimme R, Blum HE. 2011. HBV life cycle and novel drug targets. Hepatol Int 5:644-653. http://dx.doi.org/10.1007/s12072-011 -9261-3.
8. van Bömmel F, De Man RA, Wedemeyer H, Deterding K, Petersen J, Buggisch P, Erhardt A, Huppe D, Stein K, Trojan J, Sarrazin C, Bocher WO, Spengler U, Wasmuth HE, Reinders JG, Moller B, Rhode P, Feucht HH, Wiedenmann B, Berg T. 2010. Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology 51:73-80. http://dx .doi.org/10.1002/hep.23246.
9. Berg T, Zoulim F, Moeller B, Trinh H, Marcellin P, Chan S, Kitrinos KM, Dinh P, Flaherty JF, Jr, McHutchison JG, Manns M. 2014. Longterm efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients. J Hepatol 60:715-722. http://dx.doi.org/10.1016/j.jhep.2013.11.024.
10. Iwamoto M, Watashi K, Tsukuda S, Aly HH, Fukasawa M, Fujimoto A, Suzuki R, Aizaki H, Ito T, Koiwai O, Kusuhara H, Wakita T. 2014. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem Biophys Res Commun 443:808-813. http://dx.doi.org/10.1016/j.bbrc .2013.12.052.
11. Tavis JE, Gehring AJ, Hu Y. 2013. How further suppression of virus replication could improve current HBV treatment. Expert Rev Anti Infect Ther 11:755-757. http://dx.doi.org/10.1586/14787210.2013.814846.
12. Strasser SI. 2012. Drugs in development for the treatment of chronic hepatitis B. Curr Hepatitis Rep 11:111-118. http://dx.doi.org/10.1007 /s11901-012-0131-9.
13. De Clercq E, Ferir G, Kaptein S, Neyts J. 2010. Antiviral treatment of chronic hepatitis B virus (HBV) infections. Viruses 2:1279-1305. http: //dx.doi.org/10.3390/v2061279.
14. Hu Y, Cheng X, Cao F, Huang A, Tavis JE. 2013. Beta-thujaplicinol inhibits hepatitis B virus replication by blocking the viral ribonuclease H activity. Antiviral Res 99:221-229. http://dx.doi.org/10.1016/j.antiviral .2013.06.007.
15. Tavis JE, Cheng X, Hu Y, Totten M, Cao F, Michailidis E, Aurora R, Meyers MJ, Jacobsen EJ, Parniak MA, Sarafianos SG. 2013. The hepatitis B virus ribonucleaseHis sensitive to inhibitors of the human immunodeficiency virus ribonuclease H and integrase enzymes. PLoS Pathog 9:e1003125. http://dx.doi.org/10.1371/journal.ppat.1003125.
16. Cai CW, Lomonosova E, Moran EA, Cheng X, Patel KB, Bailly F, Cotelle P, Meyers MJ, Tavis JE. 2014. Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) inhibitor of the viral ribonucleaseHactivity. Antiviral Res 108:48-55. http://dx.doi .org/10.1016/j.antiviral.2014.05.007.
17. Nowotny M. 2009. Retroviral integrase superfamily: the structural perspective. EMBO Rep 10:144-151. http://dx.doi.org/10.1038/embor.2008 .256.
18. Yang W, Steitz TA. 1995. Recombining the structures of HIV integrase, RuvC and RNase H. Structure 3:131-134. http://dx.doi.org/10.1016 /S0969-2126(01)00142-3.
19. Sugawara K, Ohbayashi M, Shimizu K, Hatori M, Kamei H, Konishi M, Oki T, Kawaguchi H. 1988. BMY-28438 (3,7-dihydroxytropolone), a new antitumor antibiotic active against B16 melanoma. I. Production, isolation, structure and biological activity. J Antibiot (Tokyo) 41:862-868.
20. Meck C, D'Erasmo MP, Hirsch DR, Murelli RP. 2014. The biology and synthesis of alpha-hydroxytropolones. Medchemcomm 5:842-852. http: //dx.doi.org/10.1039/c4md00055b.
21. Chung S, Himmel DM, Jiang JK, Wojtak K, Bauman JD, Rausch JW, Wilson JA, Beutler JA, Thomas CJ, Arnold E, Le Grice SF. 2011. Synthesis, activity, and structural analysis of novel alpha-hydroxytropolone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H. J Med Chem 54:4462-4473. http://dx.doi.org/10.1021 /jm2000757.
22. Didierjean J, Isel C, Querre F, Mouscadet JF, Aubertin AM, Valnot JY, Piettre SR, Marquet R. 2005. Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H, and integrase activities by hydroxytropolones. Antimicrob Agents Chemother 49:4884-4894. http: //dx.doi.org/10.1128/AAC.49.12.4884-4894.2005.
23. Beilhartz GL, Wendeler M, Baichoo N, Rausch J, Le Grice S, Gotte M. 2009. HIV-1 reverse transcriptase can simultaneously engage its DNA/ RNA substrate at both DNA polymerase and RNase H active sites: implications for RNaseHinhibition. J Mol Biol 388:462-474. http://dx.doi.org /10.1016/j.jmb.2009.03.025.
24. Budihas SR, Gorshkova I, Gaidamakov S, Wamiru A, Bona MK, Parniak MA, Crouch RJ, McMahon JB, Beutler JA, Le Grice SF. 2005. Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones. Nucleic Acids Res 33:1249-1256. http://dx.doi.org/10.1093/nar/gki268.
25. Himmel DM, Maegley KA, Pauly TA, Bauman JD, Das K, Dharia C, Clark AD, Jr, Ryan K, Hickey MJ, Love RA, Hughes SH, Bergqvist S, Arnold E. 2009. Structure of HIV-1 reverse transcriptase with the inhibitor beta-thujaplicinol bound at the RNase H active site. Structure 17: 1625-1635. http://dx.doi.org/10.1016/j.str.2009.09.016.
26. Tavis JE, Wang H, Tollefson AE, Ying B, Korom M, Cheng X, Cao F, Davis KL, Wold WS, Morrison LA. 2014. Inhibitors of nucleotidyl transferase superfamily enzymes suppress herpes simplex virus replication. Antimicrob Agents Chemother 58:7451-7461. http://dx.doi.org/10 .1128/AAC.03875-14.
27. Iwatsuki M, Takada S, Mori M, Ishiyama A, Namatame M, Nishihara-Tsukashima A, Nonaka K, Masuma R, Otoguro K, Shiomi K, Omura S. 2011. In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A-C, produced by Penicillium sp. FKI-4410. J Antibiot (Tokyo) 64:183-188. http://dx.doi.org/10.1038/ja.2010.124.
28. Allen NE, Alborn WE, Jr, Hobbs JN, Jr, Kirst HA. 1982. 7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase. Antimicrob Agents Chemother 22:824-831. http://dx.doi.org/10 .1128/AAC.22.5.824.
29. Piettre SR, Ganzhorn A, Hoflack J, Islam K, Hornsperger J-M. 1997. Alpha-hydroxytropolones: a new class of potent inhibitors of inositol monophosphatase and other bimetallic enzymes. J Am Chem Soc 119: 3201-3204. http://dx.doi.org/10.1021/ja9634278.
30. Semenova EA, Johnson AA, Marchand C, Davis DA, Yarchoan R, Pommier Y. 2006. Preferential inhibition of the magnesium-dependent strand transfer reaction of HIV-1 integrase by alpha-hydroxytropolones. Mol Pharmacol 69:1454-1460. http://dx.doi.org/10.1124/mol.105.020321.
31. Martin SF, Follows BC, Hergenrother PJ, Franklin CL. 2000. A novel class of zinc-binding inhibitors for the phosphatidylcholine-preferring phospholipase C from Bacillus cereus. J Org Chem 65:4509-4514. http: //dx.doi.org/10.1021/jo9915731.
32. Takeshita H, Mori A, Kusaba T. 1986. An improved synthesis of 2,7-dihydroxytropone (2-hydroxytrolone). Synthesis 7:578-579.
33. Meck C, Mohd N, Murelli RP. 2012. An oxidopyrylium cyclization/ringopening route to polysubstituted alpha-hydroxytropolones. Org Lett 14: 5988-5991. http://dx.doi.org/10.1021/ol302892g.
34. Williams YD, Meck C, Mohd N, Murelli RP. 2013. Triflic acid-mediated rearrangements of 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones: synthesis of methoxytropolones and furans. J Org Chem 78:11707-11713. http://dx.doi.org/10.1021/jo401617r.
35. Hirsch DR, Cox G, D'Erasmo MP, Shakya T, Meck C, Mohd N, Wright GD, Murelli RP. 2014. Inhibition of the ANT(2")-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic alphahydroxytropolones. Bioorg Med Chem Lett 24:4943-4947. http://dx.doi .org/10.1016/j.bmcl.2014.09.037.
36. Guo H, Jiang D, Zhou T, Cuconati A, Block TM, Guo JT. 2007. Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus: an intermediate of covalently closed circular DNA formation. J Virol 81:12472-12484. http://dx.doi.org/10.1128/JVI.01123-07.
37. Gerelsaikhan T, Tavis JE, Bruss V. 1996. Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis. J Virol 70:4269-4274.
38. Li MD, Bronson DL, Lemke TD, Faras AJ. 1995. Phylogenetic analyses of 55 retroelements on the basis of the nucleotide and product amino acid sequences of the pol gene. Mol Biol Evol 12:657-670.
39. Corona A, Schneider A, Schweimer K, Rosch P, Wohrl BM, Tramontano E. 2014. Inhibition of foamy virus reverse transcriptase by human immunodeficiency virus type 1 RNase H inhibitors. Antimicrob Agents Chemother 58:4086-4093. http://dx.doi.org/10.1128/AAC.00056-14.
40. Fuji H, Urano E, Futahashi Y, Hamatake M, Tatsumi J, Hoshino T, Morikawa Y, Yamamoto N, Komano J. 2009. Derivatives of 5-nitro-furan-2-carboxylic acid carbamoylmethyl ester inhibit RNase H activity associated with HIV-1 reverse transcriptase. J Med Chem 52:1380-1387. http://dx.doi.org/10.1021/jm801071m.
41. Su HP, Yan Y, Prasad GS, Smith RF, Daniels CL, Abeywickrema PD, Reid JC, Loughran HM, Kornienko M, Sharma S, Grobler JA, Xu B, Sardana V, Allison TJ, Williams PD, Darke PL, Hazuda DJ, Munshi S. 2010. Structural basis for the inhibition of RNase H activity of HIV-1 reverse transcriptase by RNase H active site-directed inhibitors. J Virol 84:7625-7633. http://dx.doi.org/10.1128/JVI.00353-10.
42. Billamboz M, Bailly F, Lion C, Touati N, Vezin H, Calmels C, Andreola ML, Christ F, Debyser Z, Cotelle P. 2011. Magnesium chelating 2-hy-droxyisoquinoline-1,3(2H,4H)-diones, as inhibitors of HIV-1 integrase and/or the HIV-1 reverse transcriptase ribonuclease H domain: discovery of a novel selective inhibitor of the ribonuclease H function. J Med Chem 54:1812-1824. http://dx.doi.org/10.1021/jm1014692.
43. Kirschberg TA, Balakrishnan M, Squires NH, Barnes T, Brendza KM, Chen X, Eisenberg EJ, Jin W, Kutty N, Leavitt S, Liclican A, Liu Q, Liu X, Mak J, Perry JK, Wang M, Watkins WJ, Lansdon EB. 2009. RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical activity, and structural information. J Med Chem 52:5781-5784. http://dx.doi.org/10.1021/jm900597q.
44. Wendeler M, Lee HF, Bermingham A, Miller JT, Chertov O, Bona MK, Baichoo NS, Ehteshami M, Beutler J, O'Keefe BR, Gotte M, Kvaratskhelia M, Le GS. 2008. Vinylogous ureas as a novel class of inhibitors of reverse transcriptase-associated ribonuclease H activity. ACS Chem Biol 3:635-644. http://dx.doi.org/10.1021/cb8001039.
45. Himmel DM, Sarafianos SG, Dharmasena S, Hossain MM, Coy-Simandle K, Ilina T, Clark AD, Jr, Knight JL, Julias JG, Clark PK, Krogh-Jespersen K, Levy RM, Hughes SH, Parniak MA, Arnold E. 2006. HIV-1 reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl naphthyl hydrazone bound at a novel site. ACS Chem Biol 1:702-712. http://dx.doi.org/10.1021/cb600303y.
46. Zhang AX, Murelli RP, Barinka C, Michel J, Cocleaza A, Jorgensen WL, Lubkowski J, Spiegel DA. 2010. A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules. J Am Chem Soc 132:12711-12716. http://dx.doi.org /10.1021/ja104591m.
47. Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ. 2003. Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol Cell 11:807-815. http://dx.doi.org/10.1016 /S1097-2765(03)00088-1.
48. Ruhanen H, Ushakov K, Yasukawa T. 2011. Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells. Biochim Biophys Acta 1813:2000-2007. http://dx.doi.org/10 .1016/j.bbamcr.2011.08.008.
49. Wu H, Sun H, Liang X, Lima WF, Crooke ST. 2013. Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing. PLoS One 8:e71006. http://dx.doi.org/10.1371/journal.pone .0071006.
50. Nakagawa Y, Tayama K. 1998. Mechanism of mitochondrial dysfunction and cytotoxicity induced by tropolones in isolated rat hepatocytes.ChemBiol Interact 116:45-60. http://dx.doi.org/10.1016/S0009-2797(98)00078-7.
51. Chang LJ, Hirsch RC, Ganem D, Varmus HE. 1990. Effects of insertional and point mutations on the functions of the duck hepatitis B virus polymerase. J Virol 64:5553-5558.
52. Gehring A, Bertoletti A, Tavis JE. 2014. Host factor-targeted hepatitis B virus therapies. Intervirology 57:158-162. http://dx.doi.org/10.1159/000 360938.
53. Block TM, Gish R, Guo H, Mehta A, Cuconati A, Thomas London W, Guo JT. 2013. Chronic hepatitis B: what should be the goal for new therapies? Antiviral Res 98:27-34. http://dx.doi.org/10.1016/j.antiviral .2013.01.006.