Novel β-L-2'-deoxyribonucleoside Reverse Fleximers with Inhibitory Activity Against HBV, BKV, and Other Viruses

Area of Science:

• Medicinal Chemistry
• Virology
• Organic Synthesis

Background:

• L-nucleosides, like telbivudine, are effective antivirals against hepatitis B virus (HBV) but face challenges with drug resistance and limited spectrum.
• Existing L-nucleosides primarily target HBV, necessitating the development of agents with broader activity.

Purpose of the Study:

• To synthesize novel β-L-2'-deoxyribonucleoside reverse fleximer analogues.
• To evaluate the antiviral activity and toxicity profile of these new compounds across various viral families.

Main Methods:

• Chemical synthesis of a series of novel β-L-2'-deoxyribonucleoside reverse fleximers.
• In vitro antiviral assays to determine activity against human polyomavirus 1 (BK virus), HBV, flaviviruses, filoviruses, herpesviruses, and togaviruses.
• Toxicity assessments of promising compounds.

Main Results:

• Several synthesized analogues demonstrated broad-spectrum antiviral activity.
• The compound CHK-02 exhibited potent activity against BK virus (nanomolar range) and significant activity against HBV (low-micromolar range).
• CHK-02 showed moderate activity against other tested viruses with minimal observed toxicity.

Conclusions:

• L-nucleoside reverse fleximers represent a promising new class of broad-spectrum antiviral agents.
• These compounds offer potential therapeutic advantages over existing L-nucleosides due to their wider activity range and low toxicity.
• Further development of L-nucleoside reverse fleximers could lead to novel treatments for challenging viral infections.