Open AccessRemdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models
Author(s) -
Yingjun Li,
Liu Cao,
Li Ge,
Cong Feng,
Yunfeng Li,
Jing Sun,
Yinzhu Luo,
Guijiang Chen,
Guanguan Li,
Ping Wang,
Fan Xing,
Yanxi Ji,
Jincun Zhao,
Yu Zhang,
Deyin Guo,
Xumu Zhang
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.0c01929
Subject(s) - vero cell , virology , coronavirus , coronaviridae , pandemic , virus , outbreak , viral replication , ritonavir , antiviral drug , drug , mouse hepatitis virus , medicine , pharmacology , covid-19 , disease , viral load , infectious disease (medical specialty) , antiretroviral therapy
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.