瑞德西韦通过共价修饰有效抑制羧酸酯酶-2：表明存在强烈的药物相互作用。
Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions.
作者信息
Shen Yue, Eades William, Yan Bingfang
机构信息
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.
出版信息
Fundam Clin Pharmacol. 2021 Apr;35(2):432-434. doi: 10.1111/fcp.12643. Epub 2021 Jan 6.
Abstract
Remdesivir was recently approved to treat COVID-19. While this antiviral agent delivers clinical benefits, several safety concerns in many cases have been raised. This study reports that remdesivir at nanomolar concentrations inhibits carboxylesterase-2 (CES2) through covalent modifications. CES2 is a major drug-metabolizing enzyme. The combination of high potency with irreversible inhibition concludes that cautions must be exercised when remdesivir is used along with drugs hydrolyzed by CES2.
摘要
瑞德西韦最近被批准用于治疗新冠肺炎。虽然这种抗病毒药物带来了临床益处，但在许多情况下也引发了一些安全问题。本研究报告称，纳摩尔浓度的瑞德西韦通过共价修饰抑制羧酸酯酶-2（CES2）。CES2是一种主要的药物代谢酶。高效力与不可逆抑制的结合表明，当瑞德西韦与由CES2水解的药物联合使用时必须谨慎。
相似文献
1
Remdesivir potently inhibits carboxylesterase-2 through covalent modifications: signifying strong drug-drug interactions.
Fundam Clin Pharmacol. 2021 Apr;35(2):432-434. doi: 10.1111/fcp.12643. Epub 2021 Jan 6.
2
Remdesivir (Veklury) for COVID-19.
Med Lett Drugs Ther. 2020 Nov 30;62(1612):186-188.
3
Safety profile of the antiviral drug remdesivir: An update.
Biomed Pharmacother. 2020 Oct;130:110532. doi: 10.1016/j.biopha.2020.110532. Epub 2020 Jul 22.
4
What Do We Know About Remdesivir Drug Interactions?
Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26.
5
COVID-19 updates: Remdesivir (Veklury) in high-risk outpatients with COVID-19.
Med Lett Drugs Ther. 2022 Feb 21;64(1644):31-32.
6
Remdesivir (GS-5734) in COVID-19 Therapy: The Fourth Chance.
Curr Drug Targets. 2021;22(12):1346-1356. doi: 10.2174/1389450121999201202110303.
7
Remdesivir for patients with COVID-19.
CMAJ. 2021 Jan 25;193(4):E125. doi: 10.1503/cmaj.202505. Epub 2021 Jan 6.
8
Remdesivir for the treatment of COVID-19 in pregnancy.
J Med Virol. 2021 Jul;93(7):4114-4119. doi: 10.1002/jmv.26986. Epub 2021 Apr 14.
9
Remdesivir as a broad-spectrum antiviral drug against COVID-19.
Eur Rev Med Pharmacol Sci. 2021 Jan;25(1):541-548. doi: 10.26355/eurrev_202101_24426.
10
Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 1).
Ann Intern Med. 2021 Feb;174(2):229-236. doi: 10.7326/M20-5831. Epub 2020 Oct 5.
引用本文的文献
1
Carboxylesterase Factors Influencing the Therapeutic Activity of Common Antiviral Medications Used for SARS-CoV-2 Infection.
Pharmaceutics. 2025 Jun 26;17(7):832. doi: 10.3390/pharmaceutics17070832.
2
Metabolism Pathways of Major Therapeutics for Treating Monkeypox Mono- and Co-infection with Human Immunodeficient Virus or SARS-CoV-2.
Curr Drug Metab. 2023;24(4):240-249. doi: 10.2174/1389200224666230607124102.
3
Viral target and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: Molnupiravir, nirmatrelvir, and remdesivir.
Fundam Clin Pharmacol. 2023 Aug;37(4):726-738. doi: 10.1111/fcp.12889. Epub 2023 Mar 25.
4
Covalent CES2 Inhibitors Protect against Reduced Formation of Intestinal Organoids by the Anticancer Drug Irinotecan.
Curr Drug Metab. 2022;23(12):1000-1010. doi: 10.2174/1389200224666221212143904.
5
Effect of alcohol exposure on the efficacy and safety of tenofovir alafenamide fumarate, a major medicine against human immunodeficiency virus.
Biochem Pharmacol. 2022 Oct;204:115224. doi: 10.1016/j.bcp.2022.115224. Epub 2022 Aug 22.
6
The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In Vitro.
Drug Metab Dispos. 2022 Sep;50(9):1151-1160. doi: 10.1124/dmd.122.000918. Epub 2022 Jul 5.
7
Development and validation of a paper spray mass spectrometry method for the rapid quantitation of remdesivir and its active metabolite, GS-441524, in human plasma.
J Mass Spectrom Adv Clin Lab. 2022 Aug;25:27-35. doi: 10.1016/j.jmsacl.2022.06.001. Epub 2022 Jun 11.
8
The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance.
Anim Dis. 2021;1(1):15. doi: 10.1186/s44149-021-00017-5. Epub 2021 Sep 7.
9
Injectable niclosamide nanohybrid as an anti-SARS-CoV-2 strategy.
Colloids Surf B Biointerfaces. 2021 Dec;208:112063. doi: 10.1016/j.colsurfb.2021.112063. Epub 2021 Aug 24.
10
Human carboxylesterases and fluorescent probes to image their activity in live cells.
RSC Med Chem. 2021 May 18;12(7):1142-1153. doi: 10.1039/d1md00073j. eCollection 2021 Jul 21.
本文引用的文献
1
Remdesivir for the Treatment of Covid-19 - Final Report.
N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.
2
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.
Lancet. 2020 May 16;395(10236):1569-1578. doi: 10.1016/S0140-6736(20)31022-9. Epub 2020 Apr 29.
3
Compassionate Use of Remdesivir for Patients with Severe Covid-19.
N Engl J Med. 2020 Jun 11;382(24):2327-2336. doi: 10.1056/NEJMoa2007016. Epub 2020 Apr 10.
4
Covalent inhibition of carboxylesterase-2 by sofosbuvir and its effect on the hydrolytic activation of tenofovir disoproxil.
J Hepatol. 2017 Mar;66(3):660-661. doi: 10.1016/j.jhep.2016.11.025. Epub 2016 Dec 10.
5
Carboxylesterase-2 is a highly sensitive target of the antiobesity agent orlistat with profound implications in the activation of anticancer prodrugs.
Biochem Pharmacol. 2013 Feb 1;85(3):439-47. doi: 10.1016/j.bcp.2012.11.026. Epub 2012 Dec 7.
Zotero 插件