Enhanced Remdesivir Analogues to Target SARS-CoV-2

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 6; p. 2616
• Main Authors: Majima, Ryuichi, Edwards, Tiffany C, Dreis, Christine D, Geraghty, Robert J, Bonnac, Laurent F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Adenosine; Alanine - pharmacology; Alanine - therapeutic use; Amino acids; antiviral; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; C-nucleoside; Carbon; Communication; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Cytotoxicity; Drug dosages; Genomes; Glucose; Health aspects; Humans; Hybrid structures; Nucleoside analogs; Nucleosides; Pandemics; Pharmacokinetics; phosphate prodrug; Phosphorylation; RNA polymerase; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sodium; Vaccines; United States > US; SARS-CoV-2; phosphate prodrug; C-nucleoside; antiviral
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28062616

We report the short synthesis of novel -nucleoside Remdesivir analogues, their cytotoxicity and an in vitro evaluation against SARS-CoV-2 (CoV2). The described compounds are nucleoside analogues bearing a nitrogen heterocycle as purine analogues. The hybrid structures described herein are designed to enhance the anti-CoV2 activity of Remdesivir. The compounds were evaluated for their cytotoxicity and their anti-CoV2 effect. We discuss the impact of combining both sugar and base modifications on the biological activities of these compounds, their lack of cytotoxicity and their antiviral efficacy.