RT Journal Article
SR Electronic
T1 Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.26.353300
DO 10.1101/2020.10.26.353300
A1 Li, Yingjun
A1 Cao, Liu
A1 Li, Ge
A1 Cong, Feng
A1 Li, Yunfeng
A1 Sun, Jing
A1 Luo, Yinzhu
A1 Chen, Guijiang
A1 Li, Guanguan
A1 Wang, Ping
A1 Xing, Fan
A1 Ji, Yanxi
A1 Zhao, Jincun
A1 Zhang, Yu
A1 Guo, Deyin
A1 Zhang, Xumu
YR 2020
UL http://biorxiv.org/content/early/2020/10/27/2020.10.26.353300.abstract
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.