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本文引用的文献

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Physiological Mg Conditions Significantly Alter the Inhibition of HIV-1 and HIV-2 Reverse Transcriptases by Nucleoside and Non-Nucleoside Inhibitors in Vitro.生理镁离子条件在体外显著改变核苷类和非核苷类抑制剂对HIV-1和HIV-2逆转录酶的抑制作用。
Biochemistry. 2017 Jan 10;56(1):33-46. doi: 10.1021/acs.biochem.6b00943. Epub 2016 Dec 27.
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Hiv-2 molecular epidemiology.艾滋病毒2型分子流行病学
Infect Genet Evol. 2016 Dec;46:233-240. doi: 10.1016/j.meegid.2016.08.010. Epub 2016 Aug 12.
3
Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA).易位缺陷型逆转录酶抑制剂4'-乙炔基-2-氟-2'-脱氧腺苷（EFdA）抑制HIV的结构基础
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):9274-9. doi: 10.1073/pnas.1605223113. Epub 2016 Aug 3.
4
Efficient Inhibition of HIV Replication in the Gastrointestinal and Female Reproductive Tracts of Humanized BLT Mice by EFdA.EFdA对人源化BLT小鼠胃肠道和女性生殖道中HIV复制的有效抑制作用
PLoS One. 2016 Jul 20;11(7):e0159517. doi: 10.1371/journal.pone.0159517. eCollection 2016.
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Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case-series experience.膦甲酸、齐多夫定和度鲁特韦联合治疗晚期 HIV 挽救治疗的疗效和耐受性：一项病例系列研究经验。
J Med Virol. 2016 Jul;88(7):1204-10. doi: 10.1002/jmv.24442. Epub 2016 Jan 5.
6
The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.核苷类似物BMS-986001对HIV-2的体外活性比对HIV-1的活性更强。
Antimicrob Agents Chemother. 2015 Dec;59(12):7437-46. doi: 10.1128/AAC.01326-15. Epub 2015 Sep 21.
7
HIV-2EU-Supporting Standardized HIV-2 Drug-Resistance Interpretation in Europe: An Update.HIV-2EU：支持欧洲标准化的HIV-2耐药性解读：最新进展
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8
Oral administration of the nucleoside EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine) provides rapid suppression of HIV viremia in humanized mice and favorable pharmacokinetic properties in mice and the rhesus macaque.口服核苷EFdA（4'-乙炔基-2-氟-2'-脱氧腺苷）可快速抑制人源化小鼠体内的HIV病毒血症，并在小鼠和恒河猴中具有良好的药代动力学特性。
Antimicrob Agents Chemother. 2015 Jul;59(7):4190-8. doi: 10.1128/AAC.05036-14. Epub 2015 May 4.
9
In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2.多替拉韦对野生型和整合酶抑制剂耐药HIV-2的体外活性。
Retrovirology. 2015 Feb 5;12:10. doi: 10.1186/s12977-015-0146-8.
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Mutation V111I in HIV-2 reverse transcriptase increases the fitness of the nucleoside analogue-resistant K65R and Q151M viruses.HIV-2 逆转录酶中的 V111I 突变增加了核苷类似物耐药的 K65R 和 Q151M 病毒的适应性。
J Virol. 2015 Jan;89(1):833-43. doi: 10.1128/JVI.02259-14. Epub 2014 Oct 29.

MK-8591（4'-乙炔基-2-氟-2'-脱氧腺苷）在培养中对HIV-2分离株和耐药HIV-2突变体表现出强效活性。

MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture.

作者信息

Wu Vincent H, Smith Robert A, Masoum Sara, Raugi Dana N, Ba Selly, Seydi Moussa, Grobler Jay A, Gottlieb Geoffrey S

机构信息

Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.

Center for Emerging and Reemerging Infectious Diseases and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA

出版信息

Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00744-17. Print 2017 Aug.

DOI:10.1128/AAC.00744-17
PMID:28559249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5527656/
Abstract

There is a pressing need to identify more effective antiretroviral drugs for HIV-2 treatment. Here, we show that the investigational compound MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [EFdA]) is highly active against group A and B isolates of HIV-2; 50% effective concentrations [EC] for HIV-2 were, on average, 4.8-fold lower than those observed for HIV-1. MK-8591 also retains potent activity against multinucleoside-resistant HIV-2 mutants (EC ≤ 11 nM). These data suggest that MK-8591 may have antiviral activity in HIV-2-infected individuals.

摘要

迫切需要鉴定出更有效的抗逆转录病毒药物用于治疗HIV-2感染。在此，我们表明研究性化合物MK-8591（4'-乙炔基-2-氟-2'-脱氧腺苷[EFdA]）对HIV-2的A组和B组分离株具有高活性；HIV-2的50%有效浓度[EC]平均比HIV-1低4.8倍。MK-8591对多核苷耐药的HIV-2突变体也保持强效活性（EC≤11 nM）。这些数据表明MK-8591可能对HIV-2感染个体具有抗病毒活性。