Novel agents and strategies to treat herpes simplex virus infections

Expert Opinion on Investigational Drugs

Volumn 12, Issue 2, 2003, Pages 165-183

  Kleymann, Gerald ^a  

^a NONE   (Germany)

Author keywords

Antiviral agent; Disease; Drug; Herpes; HSV; Inhibitor; Simplex; Therapy; Treatment; Virus

Indexed keywords

2 ACETYLPYRIDINE 5 [(DIMETHYLAMINO)THIOCARBONYL]THIOCARBONOHYDRAZONE; 5 (2 BROMOVINYL) 2' DEOXYURIDINE; 9 [1,2 BIS(HYDROXYMETHYL)CYCLOPROPYLMETHYL]GUANINE; ACICLOVIR; ANTIVIRUS AGENT; BEHENYL ALCOHOL; CLOTRIMAZOLE; CYSTATIN C; DIMETICONE; DNA POLYMERASE; FAMCICLOVIR; FOSCARNET; HELICASE; HERPECIN; HERPES VACCINE; IDOXURIDINE; IMMUNOMODULATING AGENT; INTERFERON; INTERLEUKIN DERIVATIVE; MDL 10173; METHISOPRINOL; ORYZACYSTATIN; PENCICLOVIR; PROTEIN DERIVATIVE; TEZACITABINE; TRIFLURIDINE; UNINDEXED DRUG; VACCINIA VACCINE; VALACICLOVIR; VARICELLA ZOSTER VACCINE; VIDARABINE; VIRUS ANTIBODY; ZILACTIN B; ZILACTIN L; ZOSTEX;

ANTIVIRAL ACTIVITY; DAILY LIFE ACTIVITY; DRUG ANALYSIS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CHOICE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SAFETY; DRUG SCREENING; DRUG SPECIFICITY; DRUG TOLERABILITY; GENITAL HERPES; HERPES LABIALIS; HERPES SIMPLEX; HERPES SIMPLEX ENCEPHALITIS; HERPES SIMPLEX VIRUS 2; HIGH RISK POPULATION; HUMAN; IMMUNE DEFICIENCY; LATENT VIRUS INFECTION; NEWBORN PERIOD; NONHUMAN; PRIMARY INFECTION; PSYCHOSOCIAL DISORDER; REVIEW; SIDE EFFECT; STRUCTURE ACTIVITY RELATION; SYMPTOMATOLOGY; VIRUS REACTIVATION; VISUAL IMPAIRMENT;

ANIMALS; ANTIVIRAL AGENTS; HERPES SIMPLEX; HUMANS; SIMPLEXVIRUS; TECHNOLOGY, PHARMACEUTICAL;

EID: 0037315768     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.2.165     Document Type: Review

References (110)

1. Fields Virology (4th Edn). DM Knipe, PM Howley (Eds), Lippincott Williams & Wilkins, Philadelphia, US (2001).
2. BREN L: Genital herpes: a hidden epidemic. FDA Consum. (2002) 36(2):10-16.
3. SMITH JS, ROBINSON NJ: Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J. Infect. Dis. (2002) 186(Suppl. 1):S3-S28.
4. USTACELEBI S: Diagnosis of herpes simplex virus infections. J. Clin. Virol. (2001) 21(3):255-259.
5. ASHLEY RL. Performance and use of HSV type-specific serology test kits. Herpes (2002) 9(2):38-45.
6. CASPER C, WALD A: Condom use and the prevention of genital herpes acquisition. Herpes (2002) 9(1):10-14.
7. ZEITLIN L, WHALEY KJ: Microbicides for preventing transmission of genital herpes. Herpes (2002) 9(1):4-9.
8. STANBERRY LR, CUNNINGHAM AL, MINDEL A et al.: Prospects for control of herpes simplex virus disease through immunization. Clin. Infect. Dis. (2000) 30(3):549-566.
9. WHITLEY RJ, ROIZMAN B: Herpes simplex viruses: is a vaccine tenable? J. Clin. Invest. (2002) 110(2):145-151.
10. VANDEPAPELIERE P: Therapeutic vaccination against chronic viral infections. Lancet Infect. Dis. (2002) 2(6):353-367.
11. MORRISON LA: Vaccines against genital herpes: progress and limitations. Drugs (2002) 62(8):1119-1129.
12. STANBERRY LR, VANDEPAPELIERE P: Herpes simplex virus vaccines. In: Genital Herpes. A Volpi (Ed.), II Pensiero Scientifico Editore, Rome (In Press).
13. WHITLEY RJ: Herpes simplex vaccines. In: New Generation Vaccines. MM Levine, JB Kaper, R Rappuoli, M Liu, M Good (Eds), Marcel Dekker, Inc. New York, USA (2002) (In press).
14. COREY L, LANGENBERG AG, ASHLEY R et al.: Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group. JAMA (1999) 282(4):331-340.
15. STANBERRY LR, SPRUANCE SL, CUNNINGHAM AL et al.: Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N. Engl. J. Med. (2002) 347(21):1652-1661.
16. EO SK, PACK C, KUMARAGURU U, ROUSE BT: Optimisation of DNA vaccines for the prophylaxis and modulation of herpes simplex virus infections. Expert Opin. Biol. Ther. (2001) 1(2):213-225.
17. GERSHON AA: Live-attenuated varicella vaccine. Infect. Dis. Clin. North Am. (2001) 15(1):65-81.
18. CUNNINGHAM AL, MIKLOSKA Z: The Holy Grail: immune control of human herpes simplex virus infection and disease, Herpes (2001) 8(Suppl. 1):6A-10A.
19. FAVOREEL HW, NAUWYNCK HJ, PENSAERT MB: Immunological hiding of herpesvirus-infected cells. Arch. Virol. (2000) 145(7):1269-1290.
20. BECKER Y: Herpes simplex virus evolved to use the human defense mechanisms to establish a lifelong infection in neurons-a review and hypothesis. Virus Genes (2002) 24(2):187-196.
21. BERNSTEIN DI: Potential for immunotherapy in the treatment of herpesvirus infections. Herpes (2001) 8(1):8-11.
22. DOCKRELL DH, KINGHORN GR: Imiquimod and resiquimod as novel immunomodulators. J. Antimicrob. Chemother. (2001) 48(6):751-755.
23. STANLEY MA. Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin. Exp. Dermatol. (2002) 27(7):571-577.
24. JURK M, HEIL F, VOLLMER J et al.: Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat. Immunol. (2002) 3(6):499.
25. HEMMI H, KAISHO T, TAKEUCHI O et al.: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. (2002) 3(2):196-200.
26. SPRUANCE SL, TYRING SK, SMITH MH, MENG TC: Application of a topical immune response modifier, resiquimod gel, to modify the recurrence rate of recurrent genital herpes: a pilot study. J. Infect. Dis. (2001) 184(2):196-200.
27. DE MARIA A, TUNDO P, ROMANO A et al.: Anti-HSV-1 herpes vaccination by Lupidon H: preliminary results. Adv. Exp. Med. Biol. (1995) 371B:1599-1600.
28. CARR JA, ROGERSON J, MULQUEEN MJ, ROBERTS NA, BOOTH RF: Interleukin-12 exhibits potent antiviral activity in experimental herpesvirus infections. J. Virol. (1997) 71(10):7799-7803.
29. VOLLSTEDT S, FRANCHINI M, ALBER G, ACKERMANN M, SUTER M: Interleukin-12- and gamma interferon-dependent innate immunity are essential and sufficient for long-term survival of passively immunized mice infected with herpes simplex virus Type 1. J. Virol. (2001) 75(20):9596-9600.
30. HARANDI AM, SVENNERHOLM B, HOLMGREN J, ERIKSSON K: Interleukin-12 (IL-12) and IL-18 are important in innate defense against genital herpes simplex virus Type 2 infection in mice but are not required for the development of acquired gamma interferon-mediated protective immunity. J. Virol. (2001) 75(14):6705-6709.
31. AL-KHATIB K, CAMPBELL IL, CARR DJ: Resistance to ocular herpes simplex virus Type 1 infection in IL-12 transgenic mice. J. Neuroimmunol. (2002) 132(1-2):41-48.
32. NOISAKRAN S, CARR DJ: Type I interferons and herpes simplex virus infection: a naked DNA approach as a therapeutic option? Immunol. Res. (2001) 24(1):1-11.
33. KAUFMAN HE: Clinical cure of herpes simplex keratitis by 5-iodo-2′-deoxyuridine. Proc. Soc. Exp. Biol. Med. (1962) 109:251-252.
34. KAUFMAN HE, HEIDELBERGER C: Therapeutic antiviral action of 5-trifluoromethyl-2′-deoxyuridine. Science (1964) 145:585-586.
35. ELION GB, FURMAN PA, FYFE JA, DE MIRANDA P, BEAUCHAMP L, SCHAEFFER HJ: The selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Reproduced from Proc. Natl. Acad. Sci. USA (1977) 74:5716-5720. Rev. Med. Virol. (1999) 9(3):147-152; Discussion 152-153.
36. SCHAEFFER HJ, BEAUCHAMP L, DE MIRANDA P, ELION GB, BAUER DJ, COLLINS P: 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Nature (1978) 272(5654):583-585.
37. O'BRIEN JJ, CAMPOLI-RICHARDS DM: Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs (1989) 37(3):233-309.
38. WHITLEY RJ, GNANN JW Jr: Acyclovir: a decade later. N. Engl. J. Med. (1992) 327(11):782-789. Erratum in: N. Engl. J. Med. (1993) 328(9):671. N. Engl. J. Med. (1997) 337(23):1703.
39. BEUTNER KR: Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antiviral Res. (1995) 28(4):281-290.
40. PERRY CM, FAULDS D: Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections. Drugs (1996) 52(5):754-772.
41. BELL AR: Valaciclovir update. Adv. Exp. Med. Biol. (1999) 458:149-157.
42. JARVEST RL, SUTTON D, VERE HODGE RA: Famciclovir. Discovery and development of a novel antiherpesvirus agent. Pharm. Biotechnol. (1998) 11:313-343.
43. NAESENS L, DE CLERCQ E: Recent developments in herpesvirus therapy. Herpes (2001) 8(1):12-16.
44. VILLARREAL EC: Current and potential therapies for the treatment of herpesvirus infections. Prog. Drug Res. (2001) 56:77-120 and Spec No:185-228.
45. ABDEL-HAQ NM, ASMAR BI: Anti-herpes viruses agents. Indian J. Pediatr. (2001) 68(7):649-654.
46. WHITLEY RJ, ROIZMAN B: Herpes simplex virus infections. Lancet (2001) 357(9267):1513-1518.
47. SNOECK R: Antiviral therapy of herpes simplex. Int. J. Antimicrob. Agents (2000) 16(2):157-159.
48. SNOECK R, DE CLERCQ E: New treatments for genital herpes. Curr. Opin. Infect. Dis. (2002) 15(1):49-55.
49. WATHEN MW: Non-nucleoside inhibitors of herpesviruses. Rev. Med. Virol. (2002) 12(3):167-178.
50. YEUNG-YUE KA, BRENTJENS MH, LEE PC, TYRING SK: The management of herpes simplex virus infections. Curr. Opin. Infect. Dis. (2002) 15(2):115-122.
51. STANBERRY L, CUNNINGHAM A, MERTZ G et al.: New developments in the epidemiology, natural history and management of genital herpes. Antiviral Res. (1999) 42(1):1-14.
52. KEATING MR: Antiviral agents for non-human immunodeficiency virus infections. Mayo Clin. Proc. (1999) 74(12):1266-1283.
53. ROIZMAN B, WHITLEY RJ: The nine ages of herpes simplex virus. Herpes (2001) 8(1):23-27.
54. DE CLERCQ E, ANDREI G, SNOECK R et al.: Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents. Nucleosides Nucleotides Nucleic Acids (2001) 20(4-7):271-285.
55. GORDON YJ: The evolution of antiviral therapy for external ocular viral infections over twenty-five years. Cornea (2000) 19(5):673-680.
56. KAUFMAN HE: Treatment of viral diseases of the cornea and external eye. Prog. Retin. Eye Res. (2000) 19(1):69-85.
57. BARNARD DL: Genvir (Flamel Technologies). Curr. Opin. Investig. Drugs (2001) 2(5):622-623.
58. ALBIN R, CHASE R, RISANO C et al.: SCH 43478 and analogs: in vitro activity and in vivo efficacy of novel agents for herpesvirus Type 2. Antiviral Res. (1997) 35(3):139-146.
59. FIELD HJ: Herpes simplex virus antiviral drug resistance-current trends and future prospects. J. Clin. Virol. (2001) 21(3):261-269.
60. COLLINS P: Mechanisms of herpes virus resistance. Ann. Med. (1993) 25(5):441-445.
61. COLLINS P, DARBY G: Laboratory studies of herpes simplex virus strains resistant to acyclovir. Rev. Med. Virol. (1991) 1:19-28.
62. COEN DM: Acyclovir-resistant, pathogenic herpesviruses. Trends Microbiol. (1994) 2:481-485.
63. GILBERT C, BESTMAN-SMITH J, BOIVIN G: Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms. Drug Resist. Updates (2002) 5(2):88-114.
64. WAXMAN L, DARKE PL: The herpesvirus proteases as targets for antiviral chemotherapy. Antivir. Chem. Chemother. (2000) 11(1):1-22.
65. JARVEST RL, PINTO IL, ASHMAN SM et al.: Inhibition of herpes proteases and antiviral activity of 2-substituted thieno[2,3-d]oxazinones. Bioorg. Med. Chem. Lett. (1999) 9(3):443-448.
66. MATSUMOTO M, MISAWA S, CHIBA N, TAKAKU H, HAYASHI H: Selective nonpeptidic inhibitors of herpes simplex virus Type 1 and human cytomegalovirus proteases. Biol. Pharm. Bull. (2001) 24(3):236-241.
67. AOKI H, AKAIKE T, ABE K et al.: Antiviral effect of oryzacystatin, a proteinase inhibitor in rice, against herpes simplex virus Type 1 in vitro and in vivo. Antimicrob. Agents Chemother. (1995) 39(4):846-849.
68. BJORCK L, GRUBB A, KJELLEN L: Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus. J. Virol. (1990) 64(2):941-943.
69. OIEN NL, BRIDEAU RJ, HOPKINS TA et al.: Broad-spectrum antiherpes activities of 4-hydroxyquinoline carboxamides, a novel class of herpesvirus polymerase inhibitors. Antimicrob. Agents Chemother. (2002) 46(3):724-730.
70. BRIDEAU RJ, KNECHTEL ML, HUANG A et al.: Broad-spectrum antiviral activity of PNU-183792, a 4-oxo-dihydroquinoline, against human and animal herpesviruses. Antiviral Res. (2002) 54(1):19-28.
71. KUROKAWA M, HOZUMI T, TSURITA M, KADOTA S, NAMBA T, SHIRAKI K: Biological characterization of eugeniin as an anti-herpes simplex virus Type 1 compound in vitro and in vivo. J. Pharmacol. Exp. Ther. (2001) 297(1):372-379.
72. LIUZZI M, DEZIEL R, MOSS N et al.: A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. Nature (1994) 372(6507):695-698.
73. MOSS N, BEAULIEU P, DUCEPPE JS et al.: Peptidomimetic inhibitors of herpes simplex virus ribonucleotide reductase: a new class of antiviral agents. J. Med. Chem. (1995) 38(18):3617-3623.
74. DUAN J, LIUZZI M, PARIS W et al.: Antiviral activity of a selective ribonucleotide reductase inhibitor against acyclovir-resistant herpes simplex virus Type 1 in vivo. Antimicrob. Agents Chemother. (1998) 42(7):1629-1635.
75. BRIDGES CG, AHMED SP, SUNKARA PS, MCCARTHY JR, TYMS AS: The ribonucleotide reductase inhibitor (E)-2′-fluoromethylene-2′-deoxycytidine (MDL 101,731): a potential topical therapy for herpes simplex virus infection. Antiviral Res. (1995) 27(4):325-334.
76. SAFRIN S, SCHACKER T, DELEHANTY J, HILL E, COREY L: Topical treatment of infection with acyclovir-resistant mucocutaneous herpes simplex virus with the ribonucleotide reductase inhibitor 348U87 in combination with acyclovir. Antimicrob. Agents Chemother. (1993) 37(5):975-979.
77. SAFRIN S, SCHACKER T, DELEHANTY J, HILL E, COREY L: Potential for combined therapy with 348U87, a ribonucleotide reductase inhibitor, and acyclovir as treatment far acyclovir-resistant herpes simplex virus infection. J. Med. Virol. (1993) Suppl. 1: 146-149.
78. SPECTOR T, HARRINGTON JA, PORTER DJ: Herpes and human ribonucleotide reductases. Inhibition by 2-acetylpyridine 5-[(2-chloroanilino)-thiocarbonyl]-thiocarbonohydrazone (348U87). Biochem. Tharmacol. (1991) 42(1):91-96.
79. SPECTOR T. HARRINGTON JA, MORRISON RW et al.: 2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]-thiocarbonohydrazone (A1110U), a potent inactivator of ribonucleotide reductases of herpes simplex and varicella-zoster viruses and a potentiator of acyclovir. Proc. Natl. Acad. Sci. USA (1989) 86(3):1051-1055.
80. TURK SR, SHIPMAN C Jr, DRACH JC Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone. Biochem. Pharmacol. (1986) 35(9):1539-1545.
81. CARADONNA SJ, CHENG YC: Induction of uracil-DNA glycosylase and dUTP nucleotidohydrolase activity in herpes simplex virus-infected human cells. J. Biol. Chem. (1981) 256(19):9834-9837.
82. FOCHER F, VERRI A, SPADARI S, MANSERVIGI R, GAMBINO J, WRIGHT GE. Herpes simplex virus Type 1 uracil-DNA glycosylase: isolation and selective inhibition by novel uracil derivatives. Biochem. J. (1993) 292(Pt 3):883-889.
83. PYLES RB, THOMPSON RL: Evidence that the herpes simplex virus Type 1 uracil DNA glycosylase is required for efficient viral replication and latency in the murine nervous sysrem. J. Virol. (1994) 68(8):4963-4972.
84. SAVVA R, MCAULEY-HECHT K, BROWN T, PEARL L: The structural basis of specific base-excision repair by uracil-DNA glycosylase. Nature (1995) 373(6514):487-493.
85. SUN H, ZHI C, WRIGHT GE et al.: Molecular modeling and synthesis of inhibitors of herpes simplex virus Type 1 uracil-DNA glycosylase. J. Med. Chem. (1999) 42(13):2344-2350.
86. CHEN R, WANG H, MANSKY LM: Roles of uracil-DNA glycosylase and dUTPase in virus replication. J. Gen. Virol. (2002) 83(Pt 10):2339-2345.
87. WATKINS AM, DUNFORD PJ, MOFFATT AM et al.: Inhibition of virus-encoded thymidine kinase suppresses herpes simplex virus replication in vitro and in vivo. Antivir. Chem. Chemother. (1998) 9(1):9-18.
88. MARTIN JA, THOMAS GJ, MERRETT JH et al.: The design, synthesis and properties of highly potent and selective inhibitors of herpes simplex virus types 1 and 2 thymidine kinase. Antivir. Chem. Chemother. (1998) 9(1):1-8.
89. MARTIN JA, LAMBERT RW, MERRETT JH et al.: Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase. Bioorg. Med. Chem. Lett. (2001) 11(13):1655-1658.
90. GAUDIO AC, TAKAHATA Y, RICHARDS WG: Prediction of the binding mode of N2-phenylguanine derivative inhibitors to herpes simplex virus Type 1 thymidine kinase. J. Comput. Aided Mol. Des. (1998) 12(1):15-25.
91. XU H, MAGA G, FOCHER F et al.: Synthesis, properties, and pharmacokinetic studies of N2-phenylguanine derivatives as inhibitors of herpes simplex virus thymidine kinases. J. Med. Chem. (1995) 38(1):49-57.
92. KLEYMANN G, FISCHER R, BETZ UA et al.: New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat. Med. (2002) 8(4):392-398.
93. CRUMPACKER CS, SCHAFFER PA. New anti-HSV therapeutics target the helicase-primase complex. Nat. Med. (2002) 8(4):327-328.
94. BETZ UA, FISCHER R, KLEYMANN G, HENDRIX M, RUBSAMEN-WAIGMANN H: Potent in vivo antiviral activity of the herpes simplex virus primase-helicase inhibitor BAY 57-1293. Antimicrob. Agents Chemother. (2002) 46(6):1766-1772.
95. SPECTOR FC, LIANG L, GIORDANO H, SIVARAJA M, PETERSON MG: Inhibition of herpes simplex virus replication by a 2-amino thiazole via interactions with the helicase component of the UL5-UL8-UL52 complex. J. Virol. (1998) 72(9):6979-6987.
96. CRUTE JJ, GRYGON CA, HARGRAVE KD et al.: Herpes simplex virus helicase-primase inhibitors are active in animal models of human disease. Nat. Med. (2002) 8(4):386-391.
97. SCHANG LM, BANTLY A, KNOCKAERT M et al.: Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus Type 1 by targeting cellular, not viral, proteins. J. Virol. (2002) 76(15):7874-7882.
98. EBY GA, HALCOMB WW. Use of topical zinc to prevent recurrent herpes simplex infection: review of literature and suggested protocols. Med. Hypotheses (1985) 17(2):157-165.
99. FRANCKE B, MARGOLIN J: Effect of novobiocin and other DNA gyrase inhibitors on virus replication and DNA synthesis in herpes simplex virus Type 1-infected BHK cells. J. Gen. Virol. (1981) 52(Pt 2):401-404.
100. IKEDA S, YAZAWA M, NISHIMURA C: Antiviral activity and inhibition of topoisomerase by ofloxacin, a new quinolone derivative. Antiviral Res. (1987) 8(3):103-113.
101. WENTLAND MP PERNI RB, DORFF PH et al.: Antiviral properties of 3-quinolinecarboxamides: a series of novel non-nucleoside antiherpetic agents. Drug Des. Discov. (1997) 15(1):25-38.
102. WENTLAND MP, CARLSON JA, DORFF PH et al.: Cyclic variations of 3-quinolinecarboxamides and effects on antiherpetic activity. J. Med. Chem. (1995) 38(14):2541-2545.
103. WENTLAND MP, PERNI RB, DORFF PH et al.: 3-Quinolinecarboxamides. A series of novel orally-active antiherpetic agents. J. Med. Chem. (1993) 36(11):1580-1596.
104. AKANITAPICHAT P, LOWDEN CT, BASTOW KF: 1,3-Dihydroxyacridone derivatives as inhibitors of herpes virus replication. Antiviral Res. (2000) 45(2):123-134.
105. EBERT SN, SHTROM SS, MULLER MT: Topoisomerase II cleavage of herpes simplex virus Type 1 DNA in vivo is replication dependent. J. Virol. (1990) 64(9):4059-4066.
106. YAMADA Y, YAMAMOTO N, MAENO K, NISHIYAMA Y: Role of DNA topoisomerase I in the replication of herpes simplex virus Type 2. Arch. Virol. (1990) 110(1-2):121-127.
107. PESSINA A, MINEO E, GRIBALDO L, NERI MG: Lack of in vitro antiviral activity of fluoroquinolones against herpes simplex virus Type 2. Arch. Virol. (1992) 122(3-4):263-269.
108. NOZAWA N, DAIKOKU T, YAMAUCHI Y et al.: Identification and characterization of the UL7 gene product of herpes simplex virus Type 2. Virus Genes (2002) 24(3):257-266.
109. KLEYMANN G: Helicase-primase inhibitors. Drugs Future (2003).
110. SAWTELL NM, POON DK, TANSKY CS, THOMPSON RL: The latent herpes simplex virus Type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. J. Virol. (1998) 72(7):5343-5350.