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1
Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations.严重急性呼吸综合征冠状病毒2的联合治疗可降低莫努匹拉韦诱导的致突变性并防止对奈玛特韦/利托那韦耐药突变的选择。
J Infect Dis. 2024 Dec 16;230(6):1380-1383. doi: 10.1093/infdis/jiae213.
2
Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID-19 outcomes among outpatients: a target trial emulation investigation.奈玛特韦/利托那韦和莫努匹拉韦对门诊新冠康复者预后的疗效：一项目标试验模拟研究
Emerg Microbes Infect. 2025 Dec;14(1):2469648. doi: 10.1080/22221751.2025.2469648. Epub 2025 Mar 4.
3
Real-world effectiveness and economic analysis of nirmatrelvir/ritonavir, remdesivir, and molnupiravir for treatment of COVID-19 among ambulatory patients in Thailand.泰国门诊患者中使用奈玛特韦/利托那韦、瑞德西韦和莫努匹拉韦治疗新冠病毒病的真实世界有效性和经济分析
J Infect Public Health. 2025 Aug;18(8):102826. doi: 10.1016/j.jiph.2025.102826. Epub 2025 May 13.
4
Early use of oral antiviral drugs and the risk of post COVID-19 syndrome: A systematic review and network meta-analysis.早期使用口服抗病毒药物与新冠后综合征风险：一项系统评价和网状Meta分析
J Infect. 2024 Aug;89(2):106190. doi: 10.1016/j.jinf.2024.106190. Epub 2024 Jun 2.
5
The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19.莫努匹拉韦和奈玛特韦对重症COVID-19模型中SARS-CoV-2基因组多样性的影响。
Microbiol Spectr. 2025 May 6;13(5):e0182924. doi: 10.1128/spectrum.01829-24. Epub 2025 Mar 25.
6
Real-world effectiveness of nirmatrelvir-ritonavir and molnupiravir in non-hospitalized adults with COVID-19: a population-based, retrospective cohort study.奈玛特韦-利托那韦和莫努匹拉韦在非住院COVID-19成年患者中的真实世界疗效：一项基于人群的回顾性队列研究。
Clin Microbiol Infect. 2025 Mar;31(3):451-458. doi: 10.1016/j.cmi.2024.10.026. Epub 2024 Nov 4.
7
Oral Nirmatrelvir-Ritonavir as Postexposure Prophylaxis for Covid-19.奈玛特韦/利托那韦口服作为新冠病毒暴露后预防。
N Engl J Med. 2024 Jul 18;391(3):224-234. doi: 10.1056/NEJMoa2309002.
8
Antiviral pills could change pandemic's course.抗病毒药丸可能会改变疫情的走向。
Science. 2021 Nov 12;374(6569):799-800. doi: 10.1126/science.acx9605. Epub 2021 Nov 11.
9
Comparing the effectiveness of molnupiravir and nirmatrelvir-ritonavir in non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes: A target trial emulation study.比较莫努匹韦和奈玛特韦-利托那韦在非住院和住院 COVID-19 合并 2 型糖尿病患者中的疗效：一项目标试验模拟研究。
Diabetes Obes Metab. 2024 Oct;26(10):4653-4664. doi: 10.1111/dom.15830. Epub 2024 Aug 7.
10
[Molnupiravir or nirmatrelvir-ritonavir reduce the likelihood of hospitalization and mortality in immunocompromised patients with Covid-19.].莫努匹拉韦或奈玛特韦-利托那韦可降低新冠病毒感染免疫功能低下患者的住院和死亡风险。
Recenti Prog Med. 2024 Sep;115(9):399. doi: 10.1701/4334.43179.

引用本文的文献

1
Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses and .已获批的口服核苷类似物组合可有效抑制甲病毒和…… （原文此处不完整）
bioRxiv. 2025 Mar 11:2025.01.24.633564. doi: 10.1101/2025.01.24.633564.
2
Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2.莫努匹韦临床试验模拟表明，聚合酶链反应低估了对严重急性呼吸综合征冠状病毒2的抗病毒效力。
medRxiv. 2025 Jan 6:2024.11.21.24317726. doi: 10.1101/2024.11.21.24317726.
3
Molnupiravir in Combination With Nirmatrelvir/Ritonavir: No Cause for Alarm.莫努匹拉韦与奈玛特韦/利托那韦联用：无需担忧。
J Infect Dis. 2024 Dec 16;230(6):1297-1298. doi: 10.1093/infdis/jiae214.

本文引用的文献

1
Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses.综述：广泛人群免疫和奥密克戎谱系病毒时代下的 COVID-19 抗病毒治疗格局。
Clin Infect Dis. 2024 Apr 10;78(4):908-917. doi: 10.1093/cid/ciad685.
2
A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes.全球 SARS-CoV-2 基因组中与莫努匹韦相关的突变特征。
Nature. 2023 Nov;623(7987):594-600. doi: 10.1038/s41586-023-06649-6. Epub 2023 Sep 25.
3
Combined molnupiravir-nirmatrelvir treatment improves the inhibitory effect on SARS-CoV-2 in macaques.联合使用莫努匹韦-奈玛特韦能提高对食蟹猴体内 SARS-CoV-2 的抑制效果。
JCI Insight. 2023 Feb 22;8(4):e166485. doi: 10.1172/jci.insight.166485.
4
Unique Molecular Identifiers and Multiplexing Amplicons Maximize the Utility of Deep Sequencing To Critically Assess Population Diversity in RNA Viruses.独特分子标识符和多重扩增子最大限度地提高了深度测序在批判性评估 RNA 病毒群体多样性方面的效用。
ACS Infect Dis. 2022 Dec 9;8(12):2505-2514. doi: 10.1021/acsinfecdis.2c00319. Epub 2022 Nov 3.
5
Lethal mutagenesis as an antiviral strategy.作为抗病毒策略的致死性诱变。
Science. 2022 Feb 4;375(6580):497-498. doi: 10.1126/science.abn0048. Epub 2022 Feb 3.
6
A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.一项评估莫努匹韦在 COVID-19 患者中的 2a 期临床试验显示，其可加速 SARS-CoV-2 RNA 清除并消除具有感染性的病毒。
Sci Transl Med. 2022 Jan 19;14(628):eabl7430. doi: 10.1126/scitranslmed.abl7430.
7
β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells.β-d-N4-羟基胞苷通过致命诱变抑制 SARS-CoV-2，但对哺乳动物细胞也具有诱变作用。
J Infect Dis. 2021 Aug 2;224(3):415-419. doi: 10.1093/infdis/jiab247.
8
An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice.一种口服生物利用度的广谱抗病毒药物可抑制人呼吸道上皮细胞培养中的 SARS-CoV-2 病毒和小鼠中的多种冠状病毒。
Sci Transl Med. 2020 Apr 29;12(541). doi: 10.1126/scitranslmed.abb5883. Epub 2020 Apr 6.
9
Small-Molecule Antiviral β-d--Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance.小分子抗病毒药物 β-d--羟基胞苷能抑制未经校正的冠状病毒，该病毒对耐药性有很高的遗传屏障。
J Virol. 2019 Nov 26;93(24). doi: 10.1128/JVI.01348-19. Print 2019 Dec 15.
10
Primer ID Validates Template Sampling Depth and Greatly Reduces the Error Rate of Next-Generation Sequencing of HIV-1 Genomic RNA Populations.引物ID验证模板采样深度并大幅降低HIV-1基因组RNA群体下一代测序的错误率。
J Virol. 2015 Aug;89(16):8540-55. doi: 10.1128/JVI.00522-15. Epub 2015 Jun 3.

严重急性呼吸综合征冠状病毒2的联合治疗可降低莫努匹拉韦诱导的致突变性并防止对奈玛特韦/利托那韦耐药突变的选择。

Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations.

作者信息

Zhou Shuntai, Long Nathan, Rosenke Kyle, Jarvis Michael A, Feldmann Heinz, Swanstrom Ronald

机构信息

Lineberger Comprehensive Cancer Center.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.

出版信息

J Infect Dis. 2024 Dec 16;230(6):1380-1383. doi: 10.1093/infdis/jiae213.

DOI:10.1093/infdis/jiae213
PMID:38973065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11646606/
Abstract

We investigated the mutation profiles of severe acute respiratory syndrome coronavirus 2 in samples collected from a molnupiravir and nirmatrelvir/ritonavir combination therapy in macaques. We found that molnupiravir induced several nirmatrelvir resistance mutations at low abundance that were not further selected in combination therapy. Coadministration of nirmatrelvir/ritonavir lowered the magnitude of the mutagenetic effect of molnupiravir.

摘要

我们研究了从接受莫努匹拉韦和奈玛特韦/利托那韦联合治疗的猕猴身上采集的样本中严重急性呼吸综合征冠状病毒2的突变谱。我们发现，莫努匹拉韦诱导了几种低丰度的奈玛特韦耐药突变，这些突变在联合治疗中未被进一步选择。奈玛特韦/利托那韦的联合给药降低了莫努匹拉韦的诱变作用强度。