PT  - JOURNAL ARTICLE
AU  - Li, Yingjun
AU  - Cao, Liu
AU  - Li, Ge
AU  - Cong, Feng
AU  - Li, Yunfeng
AU  - Sun, Jing
AU  - Luo, Yinzhu
AU  - Chen, Guijiang
AU  - Li, Guanguan
AU  - Wang, Ping
AU  - Xing, Fan
AU  - Ji, Yanxi
AU  - Zhao, Jincun
AU  - Zhang, Yu
AU  - Guo, Deyin
AU  - Zhang, Xumu
TI  - Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models
AID  - 10.1101/2020.10.26.353300
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.26.353300
4099  - http://biorxiv.org/content/early/2020/10/27/2020.10.26.353300.short
4100  - http://biorxiv.org/content/early/2020/10/27/2020.10.26.353300.full
AB  - The outbreak of coronavirus disease 2019 (COVID-19) rapidly spreads across worldwide and becomes a global pandemic. Remdesivir is the only COVID-19 treatment approved by U.S. Food and Drug Administration (FDA); however, its effectiveness is still under questioning as raised by the results of a large WHO Solidarity Trial. Herein, we report that the parent nucleotide of remdesivir, GS-441524, potently inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero E6 and other cells. It exhibits good plasma distribution and longer half-life (t1/2=4.8h) in rat PK study. GS-441524 is highly efficacious against SARS-CoV-2 in AAV-hACE2 transduced mice and murine hepatitis virus (MHV) in mice, reducing the viral titers in CoV-attacked organs, without noticeable toxicity. Given that GS-441524 was the predominant metabolite of remdesivir in the plasma, the anti-COVID-19 effect of remdesivir may partly come from the effect of GS-441524. Our results also supported that GS-441524 as a promising and inexpensive drug candidate in the treatment of COVID-19 and future emerging CoVs diseases.Competing Interest StatementThe authors have declared no competing interest.