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瑞德西韦三磷酸可以有效地抑制来自各种黄病毒的 RNA 依赖性 RNA 聚合酶。

Remdesivir triphosphate can efficiently inhibit the RNA-dependent RNA polymerase from various flaviviruses.

机构信息

Institute of Organic Chemistry and Biochemistry AS CR, V.v.i., Flemingovo Nam. 2, 166 10, Prague 6, Czech Republic.

Institute of Organic Chemistry and Biochemistry AS CR, V.v.i., Flemingovo Nam. 2, 166 10, Prague 6, Czech Republic.

出版信息

Antiviral Res. 2020 Oct;182:104899. doi: 10.1016/j.antiviral.2020.104899. Epub 2020 Aug 5.

DOI:10.1016/j.antiviral.2020.104899
PMID:32763313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7403104/
Abstract

Remdesivir was shown to inhibit RNA-dependent RNA-polymerases (RdRp) from distinct viral families such as from Filoviridae (Ebola) and Coronaviridae (SARS-CoV, SARS-CoV-2, MERS). In this study, we tested the ability of remdesivir to inhibit RdRps from the Flaviviridae family. Instead of remdesivir, we used the active species that is produced in cells from remdesivir, the appropriate triphosphate, which could be directly tested in vitro using recombinant flaviviral polymerases. Our results show that remdesivir can efficiently inhibit RdRps from viruses causing severe illnesses such as Yellow fever, West Nile fever, Japanese and Tick-borne encephalitis, Zika and Dengue. Taken together, this study demonstrates that remdesivir or its derivatives have the potential to become a broad-spectrum antiviral agent effective against many RNA viruses.

摘要

瑞德西韦已被证明可抑制来自不同病毒家族的 RNA 依赖性 RNA 聚合酶（RdRp），例如丝状病毒科（埃博拉病毒）和冠状病毒科（SARS-CoV、SARS-CoV-2、MERS）。在这项研究中，我们测试了瑞德西韦抑制黄病毒科 RdRp 的能力。我们使用的是瑞德西韦在细胞中产生的活性物质，即适当的三磷酸酯，可直接使用重组黄病毒聚合酶在体外进行测试。我们的结果表明，瑞德西韦可有效抑制引起严重疾病的病毒的 RdRp，如黄热病、西尼罗河热、日本脑炎和蜱传脑炎、寨卡病毒和登革热。总之，这项研究表明，瑞德西韦或其衍生物有可能成为一种广谱抗病毒药物，对许多 RNA 病毒有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/0b6cef62d349/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/fae63670b155/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/57cfdf7d4602/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/0b6cef62d349/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/fae63670b155/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/57cfdf7d4602/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8855/7403104/0b6cef62d349/gr2_lrg.jpg

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引用本文的文献

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Mechanism of Inhibition of the Active Triphosphate Form of 2'-α-Fluoro,2'-β-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase.

ACS Infect Dis. 2025-6-13

[2]
Unlocking the potential of remdesivir: innovative approaches to drug delivery.

Drug Deliv Transl Res. 2025-4-17

[3]
Structural basis for broad-spectrum binding of AT-9010 to flaviviral methyltransferases.

Arch Virol. 2025-2-20

[4]
Enzymatic synthesis of reactive RNA probes containing squaramate-linked cytidine or adenosine for bioconjugations and cross-linking with lysine-containing peptides and proteins.

Commun Chem. 2025-1-2

[5]
Antiviral Agents: Structural Basis of Action and Rational Design.

Subcell Biochem. 2024

[6]
The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.

Vaccines (Basel). 2024-8-1

[7]
Dengue virus: pathogenesis and potential for small molecule inhibitors.

Biosci Rep. 2024-8-28

[8]
Recent advances in the study of zika virus structure, drug targets, and inhibitors.

Front Pharmacol. 2024-7-1

[9]
Mechanistic Understanding of Dexamethasone-Mediated Protection against Remdesivir-Induced Hepatotoxicity.

Mol Pharmacol. 2024-6-18

[10]
SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs.

Cell Chem Biol. 2024-4-18

本文引用的文献

[1]
Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency.

J Biol Chem. 2020-4-13

[2]
The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus.

J Biol Chem. 2020-2-24

[3]
Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.

Proc Natl Acad Sci U S A. 2020-2-13

[4]
Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase.

Antiviral Res. 2019-6-21

[5]
Structure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses.

Antiviral Res. 2019-6-13

[6]
Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir.

Viruses. 2019-4-4

[7]
The structural model of Zika virus RNA-dependent RNA polymerase in complex with RNA for rational design of novel nucleotide inhibitors.

Sci Rep. 2018-7-24

[8]
The Dengue Virus Replication Complex: From RNA Replication to Protein-Protein Interactions to Evasion of Innate Immunity.

Adv Exp Med Biol. 2018

[9]
Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses.

Antivir Chem Chemother. 2018

[10]
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses.

Sci Transl Med. 2017-6-28

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