The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models.
The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models.
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DOI：
10.3389/fphar.2021.660490
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发表时间：
2021
影响因子：
5.6
通讯作者：
Richardson A
中科院分区：
文献类型：
--
作者：
Davies SP;Mycroft-West CJ;Pagani I;Hill HJ;Chen YH;Karlsson R;Bagdonaite I;Guimond SE;Stamataki Z;De Lima MA;Turnbull JE;Yang Z;Vicenzi E;Skidmore MA;Khanim FL;Richardson A
严重急性呼吸道综合征冠状病毒-2（SARS-CoV-2）大流行已造成大量死亡和全球范围内的破坏。为了确定药物重新用于治疗SARS-CoV-2感染，我们建立了一个筛选来测量血管紧张素转换酶2（ACE2）的二聚化，ACE2是病毒的主要受体。该筛选鉴定了非诺贝特的活性代谢物非诺贝酸。在酶联免疫吸附试验（ELISA）和全细胞结合试验中，非诺贝酸还使病毒刺突蛋白的受体结合结构域（RBD）不稳定，并抑制RBD与ACE 2的结合。非诺贝特和非诺贝酸由两个独立的实验室使用两种不同的SARS-CoV-2分离株检测培养的Vero细胞的感染。在两种药物浓度下（临床上可达到），非诺贝特和非诺贝酸可将病毒感染降低高达70%。结合其广泛的临床使用历史和相对良好的安全性，本研究将非诺贝特确定为治疗SARS-CoV-2感染的潜在治疗药物，需要进行紧急临床评价。
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in enzyme-linked immunosorbent assay (ELISA) and whole cell-binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations, which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, this study identifies fenofibrate as a potential therapeutic agent requiring an urgent clinical evaluation to treat SARS-CoV-2 infection.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
DOI：
10.1016/j.bbrc.2020.11.055
发表时间：
2021-01-01
影响因子：
3.1
作者：
Lima MA;Skidmore M;Khanim F;Richardson A
通讯作者：
Richardson A
影响因子：
5.3
作者：
Desager, JP;Horsmans, Y;Harvengt, C
通讯作者：
Harvengt, C
影响因子：
3.4
作者：
Oliver, Michael
通讯作者：
Oliver, Michael
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group