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Enhanced broad spectrum in vitro antiviral efficacy of 3-F-4-MeO-Bn, 3-CN, and 4-CN derivatives of lipid remdesivir nucleoside monophosphate prodrugs.
- Source :
-
Antiviral Research . Nov2023, Vol. 219, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications. We found that 3-F-4-MeO-Bn, 3-CN-Bn, and 4-CN-Bn sn-2 glycerol modifications improved antiviral activity compared to V2043 when tested in vitro against clinically important RNA viruses from 5 virus families. These results support the continued development of V2043 and sn-2 glycerol modified RVn lipid prodrugs for the treatment of a broad range of RNA viruses for which there are limited therapies. • Lipid RVn monophosphate prodrugs are potent broad spectrum oral antivirals. • 3-F-4-MeO, 3-CN, or 4-CN modifications increase in vitro antiviral potency. • 3-F-4-MeO, 3-CN, or 4-CN modified prodrugs are active in many cell types. • These prodrugs are potent inhibitors of RNA viruses with pandemic potential. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01663542
- Volume :
- 219
- Database :
- Academic Search Index
- Journal :
- Antiviral Research
- Publication Type :
- Academic Journal
- Accession number :
- 173487245
- Full Text :
- https://doi.org/10.1016/j.antiviral.2023.105718