Comparison of anti-SARS-CoV-2 activity and intracellular metabolism of remdesivir and its parent nucleoside.

Tao, Sijia; Zandi, Keivan; Bassit, Leda; Ong, Yee Tsuey; Verma, Kiran; Liu, Peng; Downs-Bowen, Jessica A; McBrayer, Tamara; LeCher, Julia C; Kohler, James J; Tedbury, Philip R; Kim, Baek; Amblard, Franck; Sarafianos, Stefan G; Schinazi, Raymond F

Tao, Sijia; Zandi, Keivan; Bassit, Leda; Ong, Yee Tsuey; Verma, Kiran; Liu, Peng; Downs-Bowen, Jessica A; McBrayer, Tamara; LeCher, Julia C; Kohler, James J; Tedbury, Philip R; Kim, Baek; Amblard, Franck; Sarafianos, Stefan G; Schinazi, Raymond F.

Tao S; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Zandi K; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Bassit L; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Ong YT; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Verma K; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Liu P; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Downs-Bowen JA; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
McBrayer T; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
LeCher JC; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Kohler JJ; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Tedbury PR; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Kim B; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Amblard F; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Sarafianos SG; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Schinazi RF; Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Curr Res Pharmacol Drug Discov ; 2: 100045, 2021.

Article in English | MEDLINE | ID: covidwho-1351596

ABSTRACT

ABSTRACT

Remdesivir, a monophosphate prodrug of nucleoside analog GS-441524, is widely used for the treatment of moderate to severe COVID-19. It has been suggested to use GS-441524 instead of remdesivir in the clinic and in new inhalation formulations. Thus, we compared the anti-SARS-CoV-2 activity of remdesivir and GS-441524 in Vero E6, Vero CCL-81, Calu-3, Caco-2 âcells, and anti-HCoV-OC43 activity in Huh-7 âcells. We also compared the cellular pharmacology of these two compounds in Vero E6, Vero CCL-81, Calu-3, Caco-2, Huh-7, 293T, BHK-21, 3T3 and human airway epithelial (HAE) cells. Overall, remdesivir exhibited greater potency and superior intracellular metabolism than GS-441524 except in Vero E6 and Vero CCL-81 âcells.

Keywords

ACE2, angiotensin-converting enzyme 2; Anti-SARS-CoV-2; Antiviral agents; CES1, carboxylesterase 1; COVID-19; COVID-19, coronavirus disease 2019; CatA, cathepsin A; Coronavirus; DP, diphosphate; GS-441524; HAE, human airway epithelial; HCoV-OC43; HINT1, histidine triad nucleotide-binding protein 1; MP, monophosphate; NTP, nucleoside triphosphate; Pharmacology; Remdesivir; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TP, triphosphate; WHO, World Health Organization; icSARS-CoV-2-mNG, SARS-CoV-2 infectious clone virus containing mNeonGreen reporter

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Curr Res Pharmacol Drug Discov Year: 2021 Document Type: Article Affiliation country: J.crphar.2021.100045

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