E Giménez, M Guerreiro, R Gozalbo-Rovira, C Aguilar, E Albert, J L Piñana, C Solano, D Navarro
{"title":"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。","authors":"E Giménez, M Guerreiro, R Gozalbo-Rovira, C Aguilar, E Albert, J L Piñana, C Solano, D Navarro","doi":"10.37201/req/016.2023","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":21232,"journal":{"name":"Revista Espanola De Quimioterapia","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/d2/revespquimioter-36-526.PMC10586729.pdf","citationCount":"0","resultStr":"{\"title\":\"In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.\",\"authors\":\"E Giménez, M Guerreiro, R Gozalbo-Rovira, C Aguilar, E Albert, J L Piñana, C Solano, D Navarro\",\"doi\":\"10.37201/req/016.2023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":21232,\"journal\":{\"name\":\"Revista Espanola De Quimioterapia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/d2/revespquimioter-36-526.PMC10586729.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Revista Espanola De Quimioterapia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.37201/req/016.2023\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista Espanola De Quimioterapia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.37201/req/016.2023","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.
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.
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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