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Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models.
Li, Yingjun; Cao, Liu; Li, Ge; Cong, Feng; Li, Yunfeng; Sun, Jing; Luo, Yinzhu; Chen, Guijiang; Li, Guanguan; Wang, Ping; Xing, Fan; Ji, Yanxi; Zhao, Jincun; Zhang, Yu; Guo, Deyin; Zhang, Xumu.
  • Li Y; Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
  • Cao L; Medi-X, Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
  • Li G; Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
  • Cong F; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Li Y; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Sun J; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Luo Y; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Chen G; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Li G; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Wang P; Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
  • Xing F; Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
  • Ji Y; Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
  • Zhao J; Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
  • Zhang Y; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
  • Guo D; Guangdong Province Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong 510663, China.
  • Zhang X; Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
J Med Chem ; 65(4): 2785-2793, 2022 02 24.
Article in English | MEDLINE | ID: covidwho-2253698
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine / Disease Models, Animal / COVID-19 Drug Treatment Type of study: Experimental Studies / Randomized controlled trials Limits: Animals / Humans / Male Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jmedchem.0c01929

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine / Disease Models, Animal / COVID-19 Drug Treatment Type of study: Experimental Studies / Randomized controlled trials Limits: Animals / Humans / Male Language: English Journal: J Med Chem Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jmedchem.0c01929