Advancement of Prodrug Approaches for Nucleotide Antiviral Agents.
Curr Top Med Chem
; 21(32): 2909-2927, 2021.
Article
in English
| MEDLINE | ID: covidwho-1332065
ABSTRACT
Synthetic nucleoside or nucleotide analogues played a key role to the development of antiviral agents in past decades. However, low membrane permeability and insufficient cellular phosphorylation impaired the biological activity of polar nucleoside drugs because they have to penetrate the cell membrane and be phosphorylated to active metabolite stepwise by intracellular enzymes. To overcome these limitations, diverse lipophilic prodrug modifications based on nucleoside mono-, di-, and triphosphate were designed and put into practice to efficiently deliver nucleoside into the target site, and bypass the rate-limited phosphorylation step. As the most successful prodrug strategy, ProTide technology has led to the discovery of three FDA-approved antiviral agents, including sofosbuvir, tenofovir alafenadmide, and remdesivir, which has been authorized for emergency use in patients of COVID-19 in the US. In recent years, nucleoside di- and triphosphate prodrugs have also made the significant progress. This review will focus on the summary of design approach and metabolic activation path of different nucleotide prodrug strategies. The potential application of nucleotide prodrugs for the treatment of COVID-19 was also described due to the pandemic of SARS-CoV-2.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Prodrugs
/
Drug Design
/
Nucleosides
/
Nucleotides
Limits:
Humans
Language:
English
Journal:
Curr Top Med Chem
Journal subject:
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
1568026621666210728094019
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