Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models
Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models
Abstract 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.
Zhang Yu、Ji Yanxi、Zhang Xumu、Li Ge、Li Yunfeng、Sun Jing、Luo Yinzhu、Chen Guijiang、Xing Fan、Zhao Jincun、Li Guanguan、Wang Ping、Cao Liu、Li Yingjun、Guo Deyin、Cong Feng
Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteCentre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen UniversityShenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology||Medi-X, Academy for Advanced Interdisciplinary Studies, Southern University of Science and TechnologyGuangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteGuangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteGuangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring InstituteCentre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical UniversityShenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and TechnologyShenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and TechnologyCentre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen UniversityShenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology||Medi-X, Academy for Advanced Interdisciplinary Studies, Southern University of Science and TechnologyCentre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen UniversityGuangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute
药学基础医学生物科学现状、生物科学发展
GS-441524remdesivircoronavirusSARS-CoV-2MHVantiviral
Zhang Yu,Ji Yanxi,Zhang Xumu,Li Ge,Li Yunfeng,Sun Jing,Luo Yinzhu,Chen Guijiang,Xing Fan,Zhao Jincun,Li Guanguan,Wang Ping,Cao Liu,Li Yingjun,Guo Deyin,Cong Feng.Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mice Models[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/2020.10.26.353300.点此复制
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