De Clercq E
Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Biochem Pharmacol. 2007 Apr 1;73(7):911-22. doi: 10.1016/j.bcp.2006.09.014. Epub 2006 Sep 19.
Twenty years following the description of the broad-spectrum antiviral activity of S-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] [De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J, Maudgal PC. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986;323:464-7], the acyclic nucleoside phosphonates have acquired a prominent therapeutic position: (i) cidofovir in the treatment of papilloma-, herpes-, adeno- and poxvirus infections, (ii) adefovir in the treatment of chronic hepatitis B virus (HBV) infections, and (iii) tenofovir in the treatment of human immunodeficiency virus (HIV) infections (AIDS). Although formally approved only for the treatment of human cytomegalovirus (HCMV) retinitis in AIDS patients, cidofovir has been used successfully in the treatment of various other DNA virus infections, particularly human papilloma virus (HPV)-associated lesions. Adefovir dipivoxil has become a standard therapy for HBV infections, especially when resistant to lamivudine. Tenofovir disoproxil fumarate (TDF) is the corner stone of the triple-drug (TDF, emtricitabine, and efavirenz) combination therapy for AIDS, and TDF, alone or combined with emtricitabine may in the future evolve to the standard therapy of hepatitis B. Guided by the results obtained with tenofovir in the prevention of parenteral, intravaginal and perinatal infections with simian immunodeficiency virus in monkeys, and the safety profile gathered with TDF in humans with AIDS over the past 5 years since TDF was licensed for clinical use, it should be further pursued for the pre- and post-exposure prophylaxis of HIV infections in humans. Meanwhile, new classes of both acyclic (i.e. PMPO-DAPy, PMEO-DAPy, HPMPO-DAPy) and cyclic nucleoside phosphonates (i.e. PMDTA, PMDTT, GS9148) have been accredited with an antiviral potency and selectivity similar to those of cidofovir, adefovir and/or tenofovir.
在描述了S-9-(3-羟基-2-膦酰甲氧基丙基)腺嘌呤[(S)-HPMPA]的广谱抗病毒活性二十年之后[德克勒克E，霍利A，罗森伯格I，佐久间T，巴尔扎里尼J，莫德加尔PC。一种新型选择性广谱抗DNA病毒剂。《自然》1986年；323:464 - 467]，无环核苷膦酸盐已占据了显著的治疗地位：(i)西多福韦用于治疗乳头瘤病毒、疱疹病毒、腺病毒和痘病毒感染，(ii)阿德福韦用于治疗慢性乙型肝炎病毒(HBV)感染，以及(iii)替诺福韦用于治疗人类免疫缺陷病毒(HIV)感染(艾滋病)。尽管西多福韦仅被正式批准用于治疗艾滋病患者的人巨细胞病毒(HCMV)视网膜炎，但它已成功用于治疗各种其他DNA病毒感染，特别是人类乳头瘤病毒(HPV)相关病变。阿德福韦酯已成为HBV感染的标准治疗方法，尤其是对拉米夫定耐药时。替诺福韦酯(TDF)是艾滋病三联药物(TDF、恩曲他滨和依非韦伦)联合治疗的基石，并且TDF单独或与恩曲他滨联合在未来可能会发展成为乙型肝炎的标准治疗方法。受替诺福韦在预防猴经肠道、经阴道和围产期感染猿猴免疫缺陷病毒方面所获结果的指导，以及自TDF被批准用于临床使用以来过去5年在艾滋病患者中收集到的TDF安全性资料的影响，应进一步探索其在人类HIV感染暴露前和暴露后的预防作用。与此同时，新型的无环(即PMPO-DAPy、PMEO-DAPy、HPMPO-DAPy)和环状核苷膦酸盐(即PMDTA、PMDTT、GS9148)已被证实具有与西多福韦、阿德福韦和/或替诺福韦相似的抗病毒效力和选择性。
