Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models
Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models
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DOI：
10.1021/acs.jmedchem.0c01929
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发表时间：
2022-02-24
影响因子：
7.3
通讯作者：
Zhang, Xumu
中科院分区：
文献类型：
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作者：
Li, Yingjun;Cao, Liu;Zhang, Xumu
由于严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）的迅速传播，2019年冠状病毒病（COVID-19）的爆发已导致全球大流行。在本文发表时，瑞德西韦是美国食品和药物管理局批准的唯一一种COVID-19治疗药物。然而，由于世界卫生组织进行的大规模团结试验的结果，其有效性仍然受到质疑。在此，我们报告了瑞德西韦的亲本核苷GS-441524在Vero E6和其他细胞系中有效抑制SARS-CoV-2的复制。在SARS-CoV-2的AAV-hACE2小鼠模型和感染小鼠肝炎病毒（一种密切相关的冠状病毒）的小鼠中进行的攻毒研究表明，GS-441524在降低cov感染器官中的病毒滴度方面非常有效，且无明显毒性。我们的研究结果支持GS-441524是一种有前景且价格低廉的治疗COVID-19和其他CoV疾病的候选药物。
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.