Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters.
Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters.
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丙磺舒在体外和叙利亚金仓鼠体内缺乏抗病毒活性。
DOI：
10.1093/jac/dkad362
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发表时间：
2024-01-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
需要采取抗病毒干预措施，以补充疫苗接种规划并减轻COVID-19的全球负担。在开始大规模临床试验之前，需要强有力的临床前数据来支持候选药物的合理性。这项工作旨在进一步研究probenecid对SARS-CoV-2的假定抗病毒活性。感染前将Vero E6细胞与probenecid或对照培养基（SARS-CoV-2/Human/Liverpool/REMRQ0001/2020）预孵育2小时。重新涂抹Probenecid或对照培养基，再孵育，48 h后用分光光度法测定细胞病变活性。采用优化的细胞模型进行Probenecid对SARS-CoV-2-VoC-B.1.1.7 （hCoV-19/Belgium/rega-12211513/2020; EPI_ISL_791333, 2020-12-21）的体外人气道上皮细胞（HAEC）检测。叙利亚金仓鼠在治疗前24小时经鼻接种（SARS-CoV-2 Delta B.1.617.2），用probenecid或对照剂接种，每天两次，共4次。在Vero E6或HAEC试验中，probenecid没有明显的抗病毒活性。在仓鼠终末肺样本中未观察到总RNA或亚基因组RNA的减少（P > 0.05）。未感染的仓鼠体重保持稳定，而经丙烯酸酯和载药处理的感染仓鼠体重均下降（P < 0.05）。这些数据不支持probenecid作为SARS-CoV-2抗病毒药物。
Antiviral interventions are required to complement vaccination programmes and reduce the global burden of COVID-19. Prior to initiation of large-scale clinical trials, robust preclinical data to support candidate plausibility are required. This work sought to further investigate the putative antiviral activity of probenecid against SARS-CoV-2. Vero E6 cells were preincubated with probenecid, or control media for 2 h before infection (SARS-CoV-2/Human/Liverpool/REMRQ0001/2020). Probenecid or control media was reapplied, plates reincubated and cytopathic activity quantified by spectrophotometry after 48 h. In vitro human airway epithelial cell (HAEC) assays were performed for probenecid against SARS-CoV-2-VoC-B.1.1.7 (hCoV-19/Belgium/rega-12211513/2020; EPI_ISL_791333, 2020-12-21) using an optimized cell model for antiviral testing. Syrian golden hamsters were intranasally inoculated (SARS-CoV-2 Delta B.1.617.2) 24 h prior to treatment with probenecid or vehicle for four twice-daily doses. No observable antiviral activity for probenecid was evident in Vero E6 or HAEC assays. No reduction in total or subgenomic RNA was observed in terminal lung samples (P > 0.05) from hamsters. Body weight of uninfected hamsters remained stable whereas both probenecid- and vehicle-treated infected hamsters lost body weight (P > 0.5). These data do not support probenecid as a SARS-CoV-2 antiviral drug.
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影响因子：
64.8
作者：
Brevini, Teresa;Maes, Mailis;Webb, Gwilym J.;John, Binu, V;Fuchs, Claudia D.;Buescher, Gustav;Wang, Lu;Griffiths, Chelsea;Brown, Marnie L.;Scott, William E., III;Pereyra-Gerber, Pehuen;Gelson, William T. H.;Brown, Stephanie;Dillon, Scott;Muraro, Daniele;Sharp, Jo;Neary, Megan;Box, Helen;Tatham, Lee;Stewart, James;Curley, Paul;Pertinez, Henry;Forrest, Sally;Mlcochova, Petra;Varankar, Sagar S.;Darvish-Damavandi, Mahnaz;Mulcahy, Victoria L.;Kuc, Rhoda E.;Williams, Thomas L.;Heslop, James A.;Rossetti, Davide;Tysoe, Olivia C.;Galanakis, Vasileios;Vila-Gonzalez, Marta;Crozier, Thomas W. M.;Bargehr, Johannes;Sinha, Sanjay;Upponi, Sara S.;Fear, Corrina;Swift, Lisa;Saeb-Parsy, Kourosh;Davies, Susan E.;Wester, Axel;Hagstrom, Hannes;Melum, Espen;Clements, Darran;Humphreys, Peter;Herriott, Jo;Kijak, Edyta;Cox, Helen;Bramwell, Chloe;Valentijn, Anthony;Illingworth, Christopher J. R.;Dahman, Bassam;Bastaich, Dustin R.;Ferreira, Raphaella D.;Marjot, Thomas;Barnes, Eleanor;Moon, Andrew M.;Barritt, Alfred S.;Gupta, Ravindra K.;Baker, Stephen;Davenport, Anthony P.;Corbett, Gareth;Gorgoulis, Vassilis G.;Buczacki, Simon J. A.;Lee, Joo-Hyeon;Matheson, Nicholas J.;Trauner, Michael;Fisher, Andrew J.;Gibbs, Paul;Butler, Andrew J.;Watson, Christopher J. E.;Mells, George F.;Dougan, Gordon;Owen, Andrew;Lohse, Ansgar W.;Vallier, Ludovic;Sampaziotis, Fotios
通讯作者：
Sampaziotis, Fotios
DOI：
10.1002/stem.3422
发表时间：
2021-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Djidrovski I;Georgiou M;Hughes GL;Patterson EI;Casas-Sanchez A;Pennington SH;Biagini GA;Moya-Molina M;van den Bor J;Smit MJ;Chung G;Lako M;Armstrong L
通讯作者：
Armstrong L
影响因子：
6.7
作者：
Singh, Ravi Shankar P.;Toussi, Sima S.;Hackman, Frances;Chan, Phylinda L.;Rao, Rohit;Allen, Richard;Van Eyck, Lien;Pawlak, Sylvester;Kadar, Eugene P.;Clark, Frances;Shi, Haihong;Anderson, Annaliesa S.;Binks, Michael;Menon, Sandeep;Nucci, Gianluca;Bergman, Arthur
通讯作者：
Bergman, Arthur
影响因子：
120.7
作者：
Self, Wesley H.;Semler, Matthew W.;Brown, Samuel M.
通讯作者：
Brown, Samuel M.
影响因子：
13.8
作者：
Reis G;Moreira Silva EADS;Medeiros Silva DC;Thabane L;Singh G;Park JJH;Forrest JI;Harari O;Quirino Dos Santos CV;Guimarães de Almeida APF;Figueiredo Neto AD;Savassi LCM;Milagres AC;Teixeira MM;Simplicio MIC;Ribeiro LB;Oliveira R;Mills EJ;TOGETHER Investigators
通讯作者：
TOGETHER Investigators