4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication.
4'-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication.
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DOI：
10.1126/science.abj5508
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发表时间：
2022-01-14
期刊：
影响因子：
56.9
通讯作者：
Plemper, Richard K.
中科院分区：
文献类型：
--
作者：
Sourimant, Julien;Lieber, Carolin M.;Aggarwal, Megha;Cox, Robert M.;Wolf, Josef D.;Yoon, Jeong-Joong;Toots, Mart;Ye, Chengin;Sticher, Zachary;Kolykhalov, Alexander A.;Martinez-Sobrido, Luis;Bluemling, Gregory R.;Natchus, Michael G.;Painter, George R.;Plemper, Richard K.
新冠疫情凸显了研发针对呼吸道病毒的广谱疗法的迫切需求。呼吸道合胞病毒（RSV）对儿童和老年人构成重大威胁。我们介绍4'-氟尿苷（4'-FlU，EIDD - 2749），这是一种核糖核苷类似物，在细胞和人类气道上皮类器官中对RSV、相关RNA病毒以及新冠病毒（SARS - CoV - 2）具有高选择指数的抑制作用。针对RSV和新冠病毒建立的体外RNA依赖的RNA聚合酶（RdRP）检测显示，该物质掺入后会导致聚合酶抑制，进而转录停滞。在RSV感染的小鼠中，每日一次、5毫克/千克剂量的口服治疗效果显著；在感染不同新冠病毒关切变异株的雪貂中，每日一次、20毫克/千克剂量的口服治疗效果显著，分别在感染后24小时或12小时开始给药。这些特性使4'-FlU成为治疗RSV、新冠病毒及相关RNA病毒感染的广谱候选药物。
The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and human airway epithelia organoids. Polymerase inhibition within in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional stalling after incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with different SARS-CoV-2 variants-of-concern, initiated 24 or 12 hours after infection, respectively. These properties define 4′-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2, and related RNA virus infections.
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影响因子：
16.6
作者：
Kokic G;Hillen HS;Tegunov D;Dienemann C;Seitz F;Schmitzova J;Farnung L;Siewert A;Höbartner C;Cramer P
通讯作者：
Cramer P
影响因子：
7.6
作者：
Luby, Stephen P.
通讯作者：
Luby, Stephen P.
影响因子：
7.6
作者：
Painter, George R.;Bowen, Richard A.;Kolykhalov, Alexander A.
通讯作者：
Kolykhalov, Alexander A.
影响因子：
4.7
作者：
Tchesnokov, Egor P.;Feng, Joy Y.;Gotte, Matthias
通讯作者：
Gotte, Matthias
DOI：
10.1016/s0140-6736(17)30938-8
发表时间：
2017-09-02
期刊：
Lancet (London, England)
影响因子：
--
作者：
Shi T;McAllister DA;O'Brien KL;Simoes EAF;Madhi SA;Gessner BD;Polack FP;Balsells E;Acacio S;Aguayo C;Alassani I;Ali A;Antonio M;Awasthi S;Awori JO;Azziz-Baumgartner E;Baggett HC;Baillie VL;Balmaseda A;Barahona A;Basnet S;Bassat Q;Basualdo W;Bigogo G;Bont L;Breiman RF;Brooks WA;Broor S;Bruce N;Bruden D;Buchy P;Campbell S;Carosone-Link P;Chadha M;Chipeta J;Chou M;Clara W;Cohen C;de Cuellar E;Dang DA;Dash-Yandag B;Deloria-Knoll M;Dherani M;Eap T;Ebruke BE;Echavarria M;de Freitas Lázaro Emediato CC;Fasce RA;Feikin DR;Feng L;Gentile A;Gordon A;Goswami D;Goyet S;Groome M;Halasa N;Hirve S;Homaira N;Howie SRC;Jara J;Jroundi I;Kartasasmita CB;Khuri-Bulos N;Kotloff KL;Krishnan A;Libster R;Lopez O;Lucero MG;Lucion F;Lupisan SP;Marcone DN;McCracken JP;Mejia M;Moisi JC;Montgomery JM;Moore DP;Moraleda C;Moyes J;Munywoki P;Mutyara K;Nicol MP;Nokes DJ;Nymadawa P;da Costa Oliveira MT;Oshitani H;Pandey N;Paranhos-Baccalà G;Phillips LN;Picot VS;Rahman M;Rakoto-Andrianarivelo M;Rasmussen ZA;Rath BA;Robinson A;Romero C;Russomando G;Salimi V;Sawatwong P;Scheltema N;Schweiger B;Scott JAG;Seidenberg P;Shen K;Singleton R;Sotomayor V;Strand TA;Sutanto A;Sylla M;Tapia MD;Thamthitiwat S;Thomas ED;Tokarz R;Turner C;Venter M;Waicharoen S;Wang J;Watthanaworawit W;Yoshida LM;Yu H;Zar HJ;Campbell H;Nair H;RSV Global Epidemiology Network
通讯作者：
RSV Global Epidemiology Network