• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

核苷类抗病毒药物分子机制的最新进展

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.

作者信息

Kamzeeva Polina N, Aralov Andrey V, Alferova Vera A, Korshun Vladimir A

机构信息

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.

出版信息

Curr Issues Mol Biol. 2023 Aug 17;45(8):6851-6879. doi: 10.3390/cimb45080433.

DOI:10.3390/cimb45080433
PMID:37623252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10453654/
Abstract

The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs.

摘要

新病毒的出现以及已知病原体耐药菌株的出现极大地加速了新药的研发进程。核苷类似物（NAs）因其已知的安全性概况而成为一类有前景的抗病毒药物，这对于在抗击新出现病原体时快速重新利用药物很重要。研究方法的最新进展揭示了核苷类似物作用机制中一些新的意外细节，这些细节可为有效药物的进一步开发提供新方法。本综述阐述了针对病毒聚合酶的先进技术、针对新型病毒和宿主酶的靶向方法以及基于前药的抗病毒核苷类似物开发策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/fa453aca0a74/cimb-45-00433-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/f2e208331da5/cimb-45-00433-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/22bab4f67199/cimb-45-00433-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/71a232bc9d0a/cimb-45-00433-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/29d56244705f/cimb-45-00433-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/b86bd66e9e9d/cimb-45-00433-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/4faa009383bc/cimb-45-00433-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/d4b25d179e70/cimb-45-00433-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/72a256d44d7c/cimb-45-00433-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/57f6415a6877/cimb-45-00433-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/4be2822ba3ec/cimb-45-00433-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/5be9f7713712/cimb-45-00433-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/6b3ab18a8d8c/cimb-45-00433-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/dd5a7b999226/cimb-45-00433-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/dab7c2277d64/cimb-45-00433-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/d44257e2d936/cimb-45-00433-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/34e7de28aa46/cimb-45-00433-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/f25f38fc09e2/cimb-45-00433-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/5b5b5779cf14/cimb-45-00433-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/fa453aca0a74/cimb-45-00433-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/f2e208331da5/cimb-45-00433-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/22bab4f67199/cimb-45-00433-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/71a232bc9d0a/cimb-45-00433-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/29d56244705f/cimb-45-00433-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/b86bd66e9e9d/cimb-45-00433-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/4faa009383bc/cimb-45-00433-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/d4b25d179e70/cimb-45-00433-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/72a256d44d7c/cimb-45-00433-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/57f6415a6877/cimb-45-00433-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/4be2822ba3ec/cimb-45-00433-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/5be9f7713712/cimb-45-00433-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/6b3ab18a8d8c/cimb-45-00433-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/dd5a7b999226/cimb-45-00433-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/dab7c2277d64/cimb-45-00433-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/d44257e2d936/cimb-45-00433-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/34e7de28aa46/cimb-45-00433-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/f25f38fc09e2/cimb-45-00433-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/5b5b5779cf14/cimb-45-00433-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523a/10453654/fa453aca0a74/cimb-45-00433-g019.jpg

相似文献

1
Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.核苷类抗病毒药物分子机制的最新进展
Curr Issues Mol Biol. 2023 Aug 17;45(8):6851-6879. doi: 10.3390/cimb45080433.
2
Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses.SARS-CoV-2 及其他人类致病冠状病毒的抗病毒药物和可用药靶的现状。
Drug Resist Updat. 2020 Dec;53:100721. doi: 10.1016/j.drup.2020.100721. Epub 2020 Aug 26.
3
Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.核苷类和非核苷类抗病毒药物的高级前药策略：对最近五年的综述。
Molecules. 2017 Oct 16;22(10):1736. doi: 10.3390/molecules22101736.
4
Drug Repurposing Approaches for the Treatment of Influenza Viral Infection: Reviving Old Drugs to Fight Against a Long-Lived Enemy.药物重定位方法治疗流感病毒感染：用老药对抗宿敌。
Front Immunol. 2019 Mar 19;10:531. doi: 10.3389/fimmu.2019.00531. eCollection 2019.
5
A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase.核苷类似物与 SARS-CoV-2 RNA 依赖的 RNA 聚合酶相互作用的综述。
Int J Biol Macromol. 2021 Jun 30;181:605-611. doi: 10.1016/j.ijbiomac.2021.03.112. Epub 2021 Mar 22.
6
Repurposing of nucleoside- and nucleobase-derivative drugs as antibiotics and biofilm inhibitors.将核苷和核碱基衍生物药物重新用作抗生素和生物膜抑制剂。
J Antimicrob Chemother. 2017 Aug 1;72(8):2156-2170. doi: 10.1093/jac/dkx151.
7
Tissue-Specific Proteomics Analysis of Anti-COVID-19 Nucleoside and Nucleotide Prodrug-Activating Enzymes Provides Insights into the Optimization of Prodrug Design and Pharmacotherapy Strategy.抗新冠病毒核苷及核苷酸前药激活酶的组织特异性蛋白质组学分析为前药设计优化及药物治疗策略提供见解
ACS Pharmacol Transl Sci. 2021 Apr 1;4(2):870-887. doi: 10.1021/acsptsci.1c00016. eCollection 2021 Apr 9.
8
Broad-Spectrum Antiviral Strategies and Nucleoside Analogues.广谱抗病毒策略和核苷类似物。
Viruses. 2021 Apr 13;13(4):667. doi: 10.3390/v13040667.
9
Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.用于高效抗病毒药物发现的药物重新利用策略、进展与挑战
Front Pharmacol. 2021 May 4;12:660710. doi: 10.3389/fphar.2021.660710. eCollection 2021.
10
Broad-Spectrum Antiviral Activity of 3'-Deoxy-3'-Fluoroadenosine against Emerging Flaviviruses.3'-脱氧-3'-氟代腺苷对新兴黄病毒的广谱抗病毒活性。
Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi: 10.1128/AAC.01522-20.

引用本文的文献

1
The 2'-endo conformation of arabinose-CTP and arabinose-UTP inhibit viral polymerases by inducing long pauses.阿拉伯糖-CTP和阿拉伯糖-UTP的2'-内型构象通过诱导长时间停顿来抑制病毒聚合酶。
bioRxiv. 2025 Aug 26:2025.08.26.672356. doi: 10.1101/2025.08.26.672356.
2
Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.核苷酸合成的病毒重编程及其对病毒感染的影响。
J Med Virol. 2025 Aug;97(8):e70563. doi: 10.1002/jmv.70563.
3
Guanine derivatives as promising candidates for the development of purine-based antimalarial drugs.

本文引用的文献

1
Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies.细胞依赖性原药前体的激活及其在抗病毒研究中的意义。
ACS Pharmacol Transl Sci. 2023 Jul 6;6(10):1340-1346. doi: 10.1021/acsptsci.3c00050. eCollection 2023 Oct 13.
2
Nucleoside analogues: N-glycosylation methodologies, synthesis of antiviral and antitumor drugs and potential against drug-resistant bacteria and Alzheimer's disease.核苷类似物：N-糖基化方法、抗病毒和抗肿瘤药物的合成以及对抗耐药菌和阿尔茨海默病的潜力。
Carbohydr Res. 2023 Oct;532:108889. doi: 10.1016/j.carres.2023.108889. Epub 2023 Jul 17.
3
Antiviral activity of singlet oxygen-photogenerating perylene compounds against SARS-CoV-2: Interaction with the viral envelope and photodynamic virion inactivation.
鸟嘌呤衍生物作为开发嘌呤类抗疟药物的有前景的候选物。
Front Parasitol. 2025 Jul 30;4:1634209. doi: 10.3389/fpara.2025.1634209. eCollection 2025.
4
Drugs Used in the Treatment of Viral Infections for the Prevention of Airway Remodeling in Asthma.用于治疗病毒感染以预防哮喘气道重塑的药物。
Mediators Inflamm. 2025 Jul 24;2025:5526526. doi: 10.1155/mi/5526526. eCollection 2025.
5
Exploration of 4'-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents.探索4'-氟柔性聚醚核苷类似物作为潜在的广谱抗病毒药物。
Bioorg Med Chem. 2025 Oct 1;128:118243. doi: 10.1016/j.bmc.2025.118243. Epub 2025 May 20.
6
Construction and validation of a cell based reporter assay for identifying inhibitors of SARS coronavirus 2 RNA dependent RNA polymerase activity.用于鉴定严重急性呼吸综合征冠状病毒2 RNA依赖性RNA聚合酶活性抑制剂的基于细胞的报告基因检测法的构建与验证
Sci Rep. 2025 May 26;15(1):18443. doi: 10.1038/s41598-025-03813-y.
7
Novel derivatives of brincidofovir and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine inhibit orthopoxviruses and human adenoviruses more potently than brincidofovir.比昔多福韦和（S）-9-（3-羟基-2-膦酰甲氧基丙基）腺嘌呤的新型衍生物比昔多福韦更有效地抑制正痘病毒和人腺病毒。
Signal Transduct Target Ther. 2025 Apr 11;10(1):114. doi: 10.1038/s41392-025-02207-w.
8
Recent Issues in the Development and Application of Targeted Therapies with Respect to Individual Animal Variability.靶向治疗在个体动物变异性方面的开发与应用中的近期问题
Animals (Basel). 2025 Feb 6;15(3):444. doi: 10.3390/ani15030444.
9
Advances and Challenges in Antiviral Development for Respiratory Viruses.呼吸道病毒抗病毒药物研发的进展与挑战
Pathogens. 2024 Dec 31;14(1):20. doi: 10.3390/pathogens14010020.
10
Potent and Selective Human 5-HT Serotonin Receptor Antagonists: 4'-Cyano-(N)-methanocarba-adenosines by Synthetic Serendipity.强效且选择性的人5-羟色胺（5-HT）血清素受体拮抗剂：合成偶然发现的4'-氰基-（N）-甲碳环腺苷类似物。
J Med Chem. 2024 Dec 12;67(23):21264-21291. doi: 10.1021/acs.jmedchem.4c02174. Epub 2024 Nov 26.
singlet 氧光敏剂对 SARS-CoV-2 的抗病毒活性：与病毒包膜的相互作用和光动力病毒失活。
Virus Res. 2023 Sep;334:199158. doi: 10.1016/j.virusres.2023.199158. Epub 2023 Jun 29.
4
Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China.从实验室到病床：中国小分子抗 SARS-CoV-2 药物的创新。
Eur J Med Chem. 2023 Sep 5;257:115503. doi: 10.1016/j.ejmech.2023.115503. Epub 2023 May 18.
5
Prodrug Strategies for the Development of β-l-5-(()-2-Bromovinyl)-1-((2,4)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU) against Varicella Zoster Virus (VZV).β-l-5-((()-2-溴乙烯基)-1-((2,4)-2-(羟甲基)-1,3-(二氧戊环-4-基))尿嘧啶(l-BHDU)前药策略对抗水痘带状疱疹病毒(VZV)。
J Med Chem. 2023 May 25;66(10):7038-7053. doi: 10.1021/acs.jmedchem.3c00545. Epub 2023 May 4.
6
1--Octadecyl-2--benzyl--glyceryl-3--GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.1--十八烷基-2--苄基--甘油基-3--GS-441524（V2043）。在 SARS-CoV-2 感染的小鼠模型中评估口服 V2043 的效果，以及合成和评估具有增强抗 SARS-CoV-2 活性的其他磷脂酯的抗病毒活性。
J Med Chem. 2023 Apr 27;66(8):5802-5819. doi: 10.1021/acs.jmedchem.3c00046. Epub 2023 Apr 11.
7
Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA.核苷类似物通过阻断病毒聚合酶与 RNA 的相互作用来抑制 SARS-CoV-2 复制。
Int J Mol Sci. 2023 Feb 8;24(4):3361. doi: 10.3390/ijms24043361.
8
Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro.对瑞德西韦进行广泛的分析，以确定其广谱抗病毒活性和体外与其他药物相互作用的低潜力。
Sci Rep. 2023 Feb 23;13(1):3131. doi: 10.1038/s41598-023-29517-9.
9
Expanding the toolbox of metabolically stable lipid prodrug strategies.拓展代谢稳定脂质前药策略的工具库。
Front Pharmacol. 2023 Jan 6;13:1083284. doi: 10.3389/fphar.2022.1083284. eCollection 2022.
10
Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106.流感 A 型和 B 型聚合酶连续掺入核苷类似物 T1106 时的回溯直接观察。
Cell Rep. 2023 Jan 31;42(1):111901. doi: 10.1016/j.celrep.2022.111901. Epub 2023 Jan 2.