The combinatorial activities of oseltamivir and molnupiravir against influenza virus infections in vitro and in vivo

IF 2.4 3区医学 Q3 VIROLOGY

Virology Pub Date : 2025-07-24 DOI:10.1016/j.virol.2025.110642

Xili Feng , Xuanye Yang , Xinyan Hu , Qianyun Liu , Yulin Ding , Xiaoan Cao , Zhongren Ma , Xiaoxia Ma

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引用次数: 0

Abstract

Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections. However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir, a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections. In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses, when compared to oseltamivir treatment. Combination of NHC with oseltamivir exhibited a synergistic antiviral effect against the influenza A/Puerto Rico/8/34 H1N1 strain, but not the influenza B/Washington/02/2019 strain. In a mouse model infected with the PR/8 virus strain, treatment with molnupiravir alone or in combination with oseltamivir effectively attenuated lung injury and reduced viral load in the tissue. Taken together, molnupiravir can be explored in combination with oseltamivir to treat influenza, especially for patients infected with the oseltamivir-resistant strains, whereas further research is warranted.

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奥司他韦和莫那匹韦在体内和体外抗流感病毒感染的联合活性

奥司他韦是一种神经氨酸酶抑制剂，广泛用于临床治疗流感病毒感染。然而，不理想的疗效和耐药性发展的风险仍然是主要的挑战。Molnupiravir是一种核糖核苷类似物，最初是为了治疗流感而开发的，但在2021年被重新利用，并首次被批准用于治疗COVID-19。考虑到它们的互补作用模式，本研究旨在研究奥司他韦和莫硝吡韦联合抗流感病毒感染的活性。在细胞培养模型中，我们发现，与奥司他韦治疗相比，molnupiravir的活性形式β-d-N4-hydroxycytidine （NHC）对甲型和乙型流感病毒具有更强的抗病毒活性。NHC与奥司他韦联合使用对甲型流感/波多黎各/8/34 H1N1病毒株具有协同抗病毒作用，但对乙型流感/华盛顿/02/2019病毒株无协同抗病毒作用。在感染PR/8病毒株的小鼠模型中，莫诺匹拉韦单独或与奥司他韦联合治疗有效地减轻了肺损伤并降低了组织中的病毒载量。综上所提，molnupiravir可与奥司他韦联合用于治疗流感，特别是对感染了奥司他韦耐药菌株的患者，但仍需进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology 医学-病毒学

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

50 days

期刊介绍： Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.