阿昔洛韦在病毒感染和未感染细胞中的代谢。
Metabolism of acyclovir in virus-infected and uninfected cells.
作者信息
Furman P A, de Miranda P, St Clair M H, Elion G B
出版信息
Antimicrob Agents Chemother. 1981 Oct;20(4):518-24. doi: 10.1128/AAC.20.4.518.
Abstract
The metabolism of acyclovir to its mono-, di-, and triphosphate derivatives was examined in uninfected and virus-infected cells. The level of phosphorylation of acyclovir was dependent upon virus type, cell line, exogenous drug concentration, and exposure time. Acyclovir phosphorylation was inhibited by exogenously added nucleosides. The order of inhibition was deoxythymidine greater than deoxycytidine greater than guanosine greater than or equal to deoxyguanosine. Acyclovir triphosphate persisted in infected cells after removal of the drug from the medium. The initial half-life of the triphosphate was 1.2 h in the absence of the drug in the medium, but triphosphate levels reached a plateau after 6 h. The presence of low concentrations of the drug in the medium resulted in a longer persistence of the intracellular triphosphate and a higher plateau level.
摘要
在未感染和病毒感染的细胞中研究了阿昔洛韦向其一磷酸、二磷酸和三磷酸衍生物的代谢情况。阿昔洛韦的磷酸化水平取决于病毒类型、细胞系、外源药物浓度和暴露时间。外源性添加核苷可抑制阿昔洛韦的磷酸化。抑制顺序为脱氧胸苷＞脱氧胞苷＞鸟苷≥脱氧鸟苷。从培养基中去除药物后，阿昔洛韦三磷酸在感染细胞中持续存在。在培养基中不存在药物的情况下，三磷酸的初始半衰期为1.2小时，但三磷酸水平在6小时后达到平台期。培养基中低浓度药物的存在导致细胞内三磷酸的持续时间更长且平台期水平更高。
相似文献
1
Metabolism of acyclovir in virus-infected and uninfected cells.阿昔洛韦在病毒感染和未感染细胞中的代谢。
Antimicrob Agents Chemother. 1981 Oct;20(4):518-24. doi: 10.1128/AAC.20.4.518.
2
Intracellular metabolism and enzymatic phosphorylation of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and acyclovir in herpes simplex virus-infected and uninfected cells.单纯疱疹病毒感染和未感染细胞中9-(1,3-二羟基-2-丙氧甲基)鸟嘌呤和阿昔洛韦的细胞内代谢及酶促磷酸化作用
Biochem Pharmacol. 1985 Apr 1;34(7):1049-56. doi: 10.1016/0006-2952(85)90608-2.
3
Mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine against herpesviruses.（R）-9-[4-羟基-2-（羟甲基）丁基]鸟嘌呤对疱疹病毒的作用方式。
Antimicrob Agents Chemother. 1995 Aug;39(8):1802-8. doi: 10.1128/AAC.39.8.1802.
4
Effect of acyclovir on the deoxyribonucleoside triphosphate pool levels in Vero cells infected with herpes simplex virus type 1.阿昔洛韦对感染1型单纯疱疹病毒的非洲绿猴肾细胞中脱氧核苷三磷酸池水平的影响。
Am J Med. 1982 Jul 20;73(1A):14-7. doi: 10.1016/0002-9343(82)90056-0.
5
Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus.喷昔洛韦对感染1型单纯疱疹病毒（HSV-1）、2型单纯疱疹病毒（HSV-2）和水痘-带状疱疹病毒的MRC-5细胞的抗病毒作用模式
Antimicrob Agents Chemother. 1992 Dec;36(12):2747-57. doi: 10.1128/AAC.36.12.2747.
6
Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) against herpes simplex virus in MRC-5 cells.9-(4-羟基-3-羟甲基丁-1-基)鸟嘌呤（BRL 39123）在MRC-5细胞中抗单纯疱疹病毒的作用模式
Antimicrob Agents Chemother. 1989 Feb;33(2):223-9. doi: 10.1128/AAC.33.2.223.
7
Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines.阿昔洛韦[9-(2-羟乙氧甲基)鸟嘌呤]在爱泼斯坦-巴尔病毒感染的淋巴母细胞系中的磷酸化作用。
J Virol. 1981 May;38(2):606-11. doi: 10.1128/JVI.38.2.606-611.1981.
8
9
A comparison of the antiviral agents 2'-nor-2'-deoxyguanosine and acyclovir: uptake and phosphorylation in tissue culture and kinetics of in vitro inhibition of viral and cellular DNA polymerases by their respective triphosphates.抗病毒药物2'-去甲-2'-脱氧鸟苷与阿昔洛韦的比较：在组织培养中的摄取与磷酸化以及各自的三磷酸酯对病毒和细胞DNA聚合酶的体外抑制动力学
Biochem Biophys Res Commun. 1983 Oct 31;116(2):360-7. doi: 10.1016/0006-291x(83)90530-2.
10
Perspectives on interactions of acyclovir with Epstein-Barr and other herpes viruses.阿昔洛韦与爱泼斯坦-巴尔病毒及其他疱疹病毒相互作用的观点。
Am J Med. 1982 Jul 20;73(1A):18-26. doi: 10.1016/0002-9343(82)90057-2.
引用本文的文献
1
Viral proteases as therapeutic targets.病毒蛋白酶作为治疗靶点。
Mol Aspects Med. 2022 Dec;88:101159. doi: 10.1016/j.mam.2022.101159. Epub 2022 Nov 29.
2
Pathophysiological roles and therapeutic potential of voltage-gated ion channels (VGICs) in pain associated with herpesvirus infection.电压门控离子通道（VGICs）在疱疹病毒感染相关疼痛中的病理生理作用及治疗潜力
Cell Biosci. 2020 May 24;10:70. doi: 10.1186/s13578-020-00430-2. eCollection 2020.
3
Biosynthesis and half-life of MBX-2168-triphosphate in herpes virus-infected cells.疱疹病毒感染细胞中 MBX-2168-三磷酸盐的生物合成和半衰期。
Antiviral Res. 2020 Mar;175:104713. doi: 10.1016/j.antiviral.2020.104713. Epub 2020 Jan 20.
4
Retinitis associated with double infection of Epstein-Barr virus and varicella-zoster virus: A case report.与爱泼斯坦-巴尔病毒和水痘-带状疱疹病毒双重感染相关的视网膜炎：一例报告。
Medicine (Baltimore). 2018 Aug;97(31):e11663. doi: 10.1097/MD.0000000000011663.
5
A herpes simplex virus scaffold peptide that binds the portal vertex inhibits early steps in viral replication.一种单纯疱疹病毒支架肽可与核衣壳顶点结合，抑制病毒复制的早期步骤。
J Virol. 2013 Jun;87(12):6876-87. doi: 10.1128/JVI.00421-13. Epub 2013 Apr 10.
6
Glycoprotein targeted therapeutics: a new era of anti-herpes simplex virus-1 therapeutics.糖蛋白靶向治疗药物：抗单纯疱疹病毒-1 治疗的新时代。
Rev Med Virol. 2013 May;23(3):194-208. doi: 10.1002/rmv.1740. Epub 2013 Feb 26.
7
Antiviral Activity of 4'-thioIDU and Thymidine Analogs against Orthopoxviruses.4'-硫代次黄嘌呤核苷和胸苷类似物抗正痘病毒的活性。
Viruses. 2010 Sep;2(9):1968-1983. doi: 10.3390/v2091968. Epub 2010 Sep 16.
8
Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase.逆转录酶中V75I突变与HIV-1对阿昔洛韦耐药相关的机制。
J Biol Chem. 2009 Aug 7;284(32):21496-504. doi: 10.1074/jbc.M109.024026. Epub 2009 Jun 9.
9
Synthesis of the 5-phosphono-pent-2-en-1-yl nucleosides: a new class of antiviral acyclic nucleoside phosphonates.5-膦酰基-戊-2-烯-1-基核苷的合成：一类新型的抗病毒无环核苷膦酸酯。
Bioorg Med Chem. 2007 Feb 15;15(4):1771-9. doi: 10.1016/j.bmc.2006.11.038. Epub 2006 Nov 30.
10
Phosphorylation of beta-D-ribosylbenzimidazoles is not required for activity against human cytomegalovirus.β-D-核糖基苯并咪唑的磷酸化对于抗人巨细胞病毒活性并非必需。
Antimicrob Agents Chemother. 2002 Feb;46(2):478-86. doi: 10.1128/AAC.46.2.478-486.2002.
本文引用的文献
1
Inhibition of cellular alpha and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir.阿昔洛韦三磷酸盐对细胞α和病毒诱导的脱氧核糖核酸聚合酶的抑制作用。
Antimicrob Agents Chemother. 1980 Nov;18(5):741-5. doi: 10.1128/AAC.18.5.741.
2
Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)guanine] in Epstein-Barr virus-infected lymphoblastoid cell lines.阿昔洛韦[9-(2-羟乙氧甲基)鸟嘌呤]在爱泼斯坦-巴尔病毒感染的淋巴母细胞系中的磷酸化作用。
J Virol. 1981 May;38(2):606-11. doi: 10.1128/JVI.38.2.606-611.1981.
3
Acyclovir inhibition of Epstein-Barr virus replication.阿昔洛韦对EB病毒复制的抑制作用。
Proc Natl Acad Sci U S A. 1980 Sep;77(9):5163-6. doi: 10.1073/pnas.77.9.5163.
4
Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase.鸟苷酸激酶对阿昔洛韦（无环鸟苷）单磷酸的磷酸化作用。
J Biol Chem. 1980 Aug 10;255(15):7204-7.
5
Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpesvirus genetic information.阿昔洛韦对被疱疹病毒遗传信息生化转化的细胞的细胞生长和DNA合成的抑制作用。
Virology. 1980 Apr 30;102(2):420-30. doi: 10.1016/0042-6822(80)90109-9.
6
The activity in vitro against herpes virus of 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine), a new antiviral agent.
J Antimicrob Chemother. 1979 Jul;5(4):431-6. doi: 10.1093/jac/5.4.431.
7
Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate.9-(2-羟乙氧甲基)鸟嘌呤及其三磷酸酯对单纯疱疹病毒诱导的DNA聚合酶活性和病毒DNA复制的抑制作用。
J Virol. 1979 Oct;32(1):72-7. doi: 10.1128/JVI.32.1.72-77.1979.
8
Acyclovir kinetics after intravenous infusion.静脉输注后阿昔洛韦的动力学
Clin Pharmacol Ther. 1979 Dec;26(6):718-28. doi: 10.1002/cpt1979266718.
9
Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine.单纯疱疹病毒的胸苷激酶可使新型抗病毒化合物9-(2-羟乙氧甲基)鸟嘌呤发生磷酸化。
J Biol Chem. 1978 Dec 25;253(24):8721-7.
10
9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group.9-（2-羟乙氧甲基）鸟嘌呤对疱疹病毒组病毒的活性。
Nature. 1978 Apr 13;272(5654):583-5. doi: 10.1038/272583a0.
Zotero 插件