Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models

被引：89

作者：

Li, Yingjun ^{[1
,2
]}

Cao, Liu ^{[3
]}

Li, Ge ^{[4
]}

Cong, Feng ^{[4
]}

Li, Yunfeng ^{[4
]}

Sun, Jing ^{[5
]}

Luo, Yinzhu ^{[4
]}

Chen, Guijiang ^{[4
]}

Li, Guanguan ^{[1
]}

Wang, Ping ^{[1
]}

Xing, Fan ^{[3
]}

Ji, Yanxi ^{[3
]}

Zhao, Jincun ^{[5
]}

Zhang, Yu ^{[4
]}

Guo, Deyin ^{[3
]}

Zhang, Xumu ^{[1
,2
]}

机构：

[1] Southern Univ Sci & Technol, Coll Sci, Dept Chem, Shenzhen Key Lab Small Mol Drug Discovery & Synth, Shenzhen 518055, Guangdong, Peoples R China

[2] Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Medi X, Shenzhen 518055, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Ctr Infect & Immun Studies, Sch Med, Shenzhen 518107, Peoples R China

[4] Guangdong Lab Anim Monitoring Inst, Guangdong Prov Key Lab Lab Anim, Guangzhou 510663, Guangdong, Peoples R China

[5] Guangzhou Med Univ, Natl Clin Res Ctr Resp Dis, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou 510182, Guangdong, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2022年 / 65卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ANTIVIRAL ACTIVITY; TISSUE-CULTURE; VIRUS; CORONAVIRUS; PRODRUG; MECHANISM; EFFICACY; GS-5734; EBOLA;

D O I：

10.1021/acs.jmedchem.0c01929

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in a global pandemic due to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the time of this manuscript's publication, remdesivir is the only COVID-19 treatment approved by the United States Food and Drug Administration. However, its effectiveness is still under question due to the results of the large Solidarity Trial conducted by the World Health Organization. Herein, we report that the parent nucleoside of remdesivir, GS-441524, potently inhibits the replication of SARS-CoV-2 in Vero E6 and other cell lines. Challenge studies in both an AAV-hACE2 mouse model of SARS-CoV-2 and in mice infected with murine hepatitis virus, a closely related coronavirus, showed that GS-441524 was highly efficacious in reducing the viral titers in CoV-infected organs without notable toxicity. Our results support that GS-441524 is a promising and inexpensive drug candidate for treating of COVID-19 and other CoV diseases.

引用

页码：2785 / 2793

页数：9

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