Antiviral activity of aliphatic nucleoside analogues: structure-function relationship

Area of Science:

• Virology
• Medicinal Chemistry
• Nucleoside Analogues

Background:

• Nucleoside analogues are investigated for antiviral properties.
• Aliphatic nucleoside analogues offer diverse chemical structures for drug discovery.
• Viral infections necessitate the development of novel antiviral agents.

Purpose of the Study:

• To identify potent antiviral agents from a series of aliphatic nucleoside analogues.
• To evaluate the antiviral efficacy of (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] and related compounds.
• To determine the inhibitory concentrations of active analogues against specific viruses.

Main Methods:

• Synthesis and screening of 58 aliphatic nucleoside analogues.
• Antiviral assays using primary rabbit kidney cell cultures.
• Challenging cell cultures with vaccinia virus and vesicular stomatitis virus.
• Determining effective concentrations for viral replication inhibition.

Main Results:

• (S)-DHPA demonstrated the highest antiviral activity among the tested analogues.
• (S)-DHPA inhibited vaccinia and vesicular stomatitis virus replication at 0.05-0.1 mM.
• Other analogues showed limited or no antiviral activity at 2 mM, with some exceptions at 0.5-1 mM.

Conclusions:

• (S)-DHPA is a highly promising antiviral candidate for vaccinia and vesicular stomatitis viruses.
• The structural features of (S)-DHPA contribute to its potent antiviral effects.
• Further research into DHPA analogues may yield broader-spectrum antiviral therapies.