In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.

IF 1.9 4区 医学 Q4 MICROBIOLOGY
Revista Espanola De Quimioterapia Pub Date : 2023-10-01 Epub Date: 2023-06-28 DOI:10.37201/req/016.2023
E Giménez, M Guerreiro, R Gozalbo-Rovira, C Aguilar, E Albert, J L Piñana, C Solano, D Navarro
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引用次数: 0

Abstract

Objective: Letermovir (LMV) is used for prophylaxis of cytomegalovirus (CMV) reactivation and end-organ disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). In turn, sirolimus (SLM) which displays in vitro anti-CMV activity, is frequently employed for prophylaxis of Graft vs. Host disease in allo-HSCT. Here, we aimed at assessing whether LMV and SLM used in combination may act synergistically in vitro on inhibiting CMV replication.

Methods: The antiviral activity of LMV and SLM alone or in combination was evaluated by a checkerboard assay, using ARPE-19 cells infected with CMV strain BADrUL131-Y. LMV and SLM were used at concentrations ranging from 24 nM to 0.38 nM and 16 nM to 0.06 nM, respectively.

Results: The mean EC50 for LMV and SLM was 2.44 nM (95% CI, 1.66-3.60) and 1.40 nM (95% CI, 0.41-4.74), respective. LMV and SLM interaction yielded mainly additive effects over the range of concentrations tested.

Conclusions: The additive nature of the combination of LMV and SLM against CMV may have relevant clinical implications in management of CMV infection in allo-HSCT recipients undergoing prophylaxis with LMV.

Abstract Image

Abstract Image

来特莫韦和西罗莫司对巨细胞病毒复制的联合作用的体外评估。
目的:莱特莫韦(LMV)用于预防成人巨细胞病毒血清阳性异基因造血干细胞移植受者(allo-HSCT)的巨细胞病毒(CMV)再激活和末端器官疾病。反过来,显示出体外抗CMV活性的西罗莫司(SLM)经常用于预防同种异体造血干细胞移植中的移植物抗宿主病。在此,我们旨在评估LMV和SLM联合使用是否可以在体外协同抑制CMV复制。方法:利用感染CMV BADrUL131-Y株的ARPE-19细胞,通过棋盘格分析法评估LMV和SLM单独或联合的抗病毒活性。LMV和SLM分别以24nM至0.38nM和16nM至0.06nM的浓度使用。结果:LMV和SLM的平均EC50分别为2.44nM(95%CI,1.66-3.60)和1.40nM(95%CI,0.41-4.74)。LMV和SLM相互作用在测试的浓度范围内主要产生相加效应。结论:LMV和SLM联合对抗CMV的加性性质可能对接受LMV预防的异基因造血干细胞移植受者的CMV感染管理具有相关的临床意义。
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来源期刊
CiteScore
2.90
自引率
10.50%
发文量
146
审稿时长
>12 weeks
期刊介绍: The official journal of the Sociedad Española de Quimioterapia (Spanish Society of Chemotherapy), publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents primarily in human medicine. Authors sign an exclusive license agreement, where authors have copyright but license exclusive rights in their article to the Publisher. All manuscripts are free open access. Revista Española de Quimioterapia includes the following sections: reviews, original articles, brierf reports, letters, and consensus documents.
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