Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years
Date
2017-10-16
Authors
Sinokrot, Hanadi
Smerat, Tasneem
Najjar, Anas
Karaman, Rafik
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks
from which currently used antiviral agents suffer, thus make them excellent targets for research,
especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies
employed in the studies covered in this review were sorted by the type of drug synthesized into ester
prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and
non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug
was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug
zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally,
VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing
clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular,
protides and nucleoside analogues, and non-nucleoside analogues prodrugs), the most promising are
nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works
by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues
have witnessed productive era in the recent past few years. The era of non-interferon based treatment
of hepatitis (through direct inhibitors of NS5A) has dawned.
Description
Keywords
antiviral , macromolecules , prodrug , nucleoside , non-nucleoside , protide , targeted delivery