国际口腔医学杂志 ›› 2018, Vol. 45 ›› Issue (3): 351-357.doi: 10.7518/gjkq.2018.03.020

• 综述 • 上一篇    下一篇

核苷类抗疱疹病毒药物的研究进展

吉宁, 赵行, 曾昕, 陈谦明   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院 成都 610041
  • 收稿日期:2017-10-09 修回日期:2018-01-30 发布日期:2018-05-08
  • 通讯作者: 赵行,副教授,博士,Email:zhaohangahy@scu.edu.cn
  • 作者简介:吉宁,实验师,硕士,Email:jining_1023@126.com
  • 基金资助:
    国家自然科学基金(81621062,81500860)

Research progress on nucleoside drugs against herpes virus

Ji Ning, Zhao Hang, Zeng Xin, Chen Qianming   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2017-10-09 Revised:2018-01-30 Published:2018-05-08
  • Supported by:
    This study was supported by National Natural Science Foundation of China (81621062, 81500860).

摘要: 疱疹病毒可引起多种疾病,如角膜炎、唇疱疹、带状疱疹、生殖器疱疹、脑炎等,目前临床上用于治疗疱疹性疾病的药物主要是以阿昔洛韦为代表的核苷类药物,本文对已上市及正在研究中的核苷类抗疱疹药物及其作用机制作简要介绍。

关键词: 疱疹病毒, 核苷类药物, 作用机制

Abstract: Herpes virus can cause many diseases, such as keratitis, cold sores, herpes zoster, genital herpes, and encephalitis, etc. Aciclovir and related nucleoside analogues are gold standard molecules for treatment of herpetic diseases in clinical over the past decades. Here, the recent progress of anti-herpes virus nucleoside agents are summarized in this review, including structure characteristic, antiviral mechanism and clinical application.

Key words: herpes virus, nucleoside drugs, mechanism

中图分类号: 

  • R97
[1] Dreyfus DH.Herpesviruses and the microbiome[J]. J Allergy Clin Immunol, 2013, 132(6):1278-1286.
[2] Suazo PA, Ibañez FJ, Retamal-Díaz AR, et al.Evasion of early antiviral responses by herpes simplex viruses[J]. Mediators Inflamm, 2015, 2015:593757.
[3] Galdiero S, Falanga A, Tarallo R, et al.Peptide inhi-bitors against herpes simplex virus infections[J]. J Pept Sci, 2013, 19(3):148-158.
[4] Zis P, Stritsou P, Angelidakis P, et al.Herpes simplex virus type 2 encephalitis as a cause of ischemic stroke: case report and systematic review of the literature[J]. J Stroke Cerebrovasc Dis, 2016, 25(2):335-339.
[5] Conrady CD, Drevets DA, Carr DJ.Herpes simplex type Ⅰ (HSV-1) infection of the nervous system: is an immune response a good thing[J]. J Neuroimmu-nol, 2010, 220(1/2):1-9.
[6] Harris SA, Harris EA.Herpes simplex virus type 1 and other pathogens are key causative factors in sporadic Alzheimer’s disease[J]. J Alzheimers Dis, 2015, 48(2):319-353.
[7] Zarrouk K, Piret J, Boivin G.Herpesvirus DNA poly-merases: structures, functions and inhibitors[J]. Virus Res, 2017, 234:177-192.
[8] De Clercq E.Antivirals: past, present and future[J]. Biochem Pharmacol, 2013, 85(6):727-744.
[9] De Clercq E, Holý A.Acyclic nucleoside phospho-nates: a key class of antiviral drugs[J]. Nat Rev Drug Discov, 2005, 4(11):928-940.
[10] De Clercq E.The discovery of antiviral agents: ten different compounds, ten different stories[J]. Med Res Rev, 2008, 28(6):929-953.
[11] Jiang YC, Feng H, Lin YC, et al.New strategies against drug resistance to herpes simplex virus[J]. Int J Oral Sci, 2016, 8(1):1-6.
[12] Hornig J, McGregor A. Design and development of antivirals and intervention strategies against human herpesviruses using high-throughput approach[J]. Expert Opin Drug Discov, 2014, 9(8):891-915.
[13] Whitley RJ, Roizman B.Herpes simplex virus infec-tions[J]. Lancet, 2001, 357(9267):1513-1518.
[14] Gilbert C, Bestman-Smith J, Boivin G.Resistance of herpesviruses to antiviral drugs: clinical impacts and molecular mechanisms[J]. Drug Resist Updat, 2002, 5(2):88-114.
[15] Prusoff WH.Synthesis and biological activities of iododeoxyuridine, an analog of thymidine[J]. Biochim Biophys Acta, 1959, 32(1):295-296.
[16] De Clercq E.Chapter 1 Looking back in 2009 at the dawning of antiviral therapy now 50 years ago[J]. Adv Virus Res, 2009, 73:1-53.
[17] Kaufman HE.Clinical cure of herpes simplex kera-titis by 5-iodo-2-deoxyuridine[J]. Proc Soc Exp Biol Med, 1962, 109:251-252.
[18] Kaufman HE, Heidelberger C.Therapeutic antiviral action of 5-trifluoromethyl-2’-deoxyuridine in herpes simplex keratitis[J]. Sci, 1964, 145(3632):585-586.
[19] Whitley RJ, Ch’ien LT, Dolin R, et al.Adenine arab-inoside therapy of herpes zoster in the immunosup-pressed. NIAID collaborative antiviral study[J]. N Engl J Med, 1976, 294(22):1193-1199.
[20] Whitley RJ, Soong SJ, Dolin R, et al.Adenine arab-inoside therapy of biopsy-proved herpes simplex en-cephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study[J]. N Engl J Med, 1977, 297(6):289-294.
[21] Whitley R, Arvin A, Prober C, et al.A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection[J]. N Engl J Med, 1991, 324(7):444-449.
[22] Elion GB, Furman PA, Fyfe JA, et al.Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine[J]. Proc Natl Acad Sci USA, 1977, 74(12):5716-5720.
[23] Schaeffer HJ, Beauchamp L, de Miranda P, et al. 9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group[J]. Nature, 1978, 272(5654):583-585.
[24] Erice A, Chou S, Biron KK, et al.Progressive disease due to ganciclovir-resistant cytomegalovirus in im-munocompromised patients[J]. N Engl J Med, 1989, 320(5):289-293.
[25] Gnann JW Jr, Crumpacker CS, Lalezari JP, et al.Sori-vudine versus acyclovir for treatment of dermatomal herpes zoster in human immunodeficiency virus-in-fected patients: results from a randomized, controlled clinical trial. Collaborative Antiviral Study Group/AIDS Clinical Trials Group, Herpes Zoster Study Group[J]. Antimicrob Agents Chemother, 1998, 42(5):1139-1145.
[26] Perry CM, Faulds D.Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections[J]. Drugs, 1996, 52(5):754-772.
[27] Haynes P, Lambert TR, Mitchell ID.Comparative in-vivo genotoxicity of antiviral nucleoside analogues; penciclovir, acyclovir, ganciclovir and the xanthine analogue, caffeine, in the mouse bone marrow micro-nucleus assay[J]. Mutat Res, 1996, 369(1/2):65-74.
[28] Perry CM, Wagstaff AJ.Famciclovir. A review of its pharmacological properties and therapeutic efficacy in herpesvirus infections[J]. Drugs, 1995, 50(2):396-415.
[29] Field HJ, Tewari D, Sutton D, et al.Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosup-pression model[J]. Antimicrob Agents Chemother, 1995, 39(5):1114-1119.
[30] Lea AP, Bryson HM.Cidofovir[J]. Drugs, 1996, 52(2):225-231.
[31] Ciancio G, Burke GW, Mattiazzi A, et al.Cytomega-lovirus prophylaxis with valganciclovir in kidney, pancreas-kidney, and pancreas transplantation[J]. Clin Transplant, 2004, 18(4):402-406.
[32] Boivin G, Goyette N, Gilbert C, et al.Absence of cytomegalovirus-resistance mutations after valganci-clovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients[J]. J Infect Dis, 2004, 189(9):1615-1618.
[33] Deeks SG, Collier A, Lalezari J, et al.The safety and efficacy of adefovir dipivoxil, a novel anti-human im-munodeficiency virus (HIV) therapy, in HIV-infected adults: a randomized, double-blind, placebo-controlled trial[J]. J Infect Dis, 1997, 176(6):1517-1523.
[34] Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al.Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B[J]. N Engl J Med, 2003, 348(9):800-807.
[35] Ramsay ID, Attwood C, Irish D, et al.Disseminated adenovirus infection after allogeneic stem cell trans-plant and the potential role of brincidofovir-Case series and 10 year experience of management in an adult transplant cohort[J]. J Clin Virol, 2017, 96:73-79.
[36] Lederman ER, Davidson W, Groff HL, et al.Progre-ssive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001[J]. J Infect Dis, 2012, 206(9):1372-1385.
[37] Toth K, Tollefson AE, Spencer JF, et al.Combina-tion therapy with brincidofovir and valganciclovir against species C adenovirus infection in the immunosu-ppressed Syrian hamster model allows for substantial reduction of dose for both compounds[J]. Antiviral Res, 2017, 146:121-129.
[38] Quenelle DC, Kern ER.Treatment of vaccinia and cowpox virus infections in mice with CMX001 and ST-246[J]. Viruses, 2010, 2(12):2681-2695.
[39] De Clercq E.Highly potent and selective inhibition of varicella-zoster virus replication by bicyclic furo-[2,3-d]pyrimidine nucleoside analogues[J]. Med Res Rev, 2003, 23(3):253-274.
[40] De Clercq E.Selective anti-herpesvirus agents[J]. Antivir Chem Chemother, 2013, 23(3):93-101.
[41] Migliore M.FV-100: the most potent and selective anti-varicella zoster virus agent reported to date[J]. Antivir Chem Chemother, 2010, 20(3):107-115.
[42] Pentikis HS, Matson M, Atiee G, et al.Pharmacoki-netics and safety of FV-100, a novel oral anti-herpes zoster nucleoside analogue, administered in single and multiple doses to healthy young adult and elderly adult volunteers[J]. Antimicrob Agents Chemother, 2011, 55(6):2847-2854.
[43] Andrei G, Snoeck R.Advances in the treatment of varicella-zoster virus infections[J]. Antiviral Agents, 2013, 67:107-168.
[44] Krecmerova M.Amino acid ester prodrugs of nucleo-side and nucleotide antivirals[J]. Mini Rev Med Chem, 2017, 17(10):818-833.
[45] De SK, Hart JC, Breuer J.Herpes simplex virus and varicella zoster virus: recent advances in therapy[J]. Curr Opin Infect Dis, 2015, 28(6):589-595.
[46] Tyring SK, Plunkett S, Scribner AR, et al.Valoma-ciclovir versus valacyclovir for the treatment of acute herpes zoster in immunocompetent adults: a rando-mized, double-blind, active-controlled trial[J]. J Med Virol, 2012, 84(8):1224-1232.
[47] Price NB, Prichard MN.Progress in the development of new therapies for herpesvirus infections[J]. Curr Opin Virol, 2011, 1(6):548-554.
[48] Houldcroft CJ, Bryant JM, Depledge DP, et al.Detec-tion of low frequency multi-drug resistance and novel putative maribavir resistance in immunocompromised pediatric patients with cytomegalovirus[J]. Front Mic-robiol, 2016, 7:1317.
[49] Bright PD, Gompels M, Donati M, et al.Successful oral treatment of Ganciclovir resistant cytomegalo-virus with Maribavir in the context of primary immuno-deficiency: first case report and review[J]. J Clin Virol, 2017, 87:12-16.
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