Heli-SMACC: Helicase-targeting SMAll Molecule Compound Collection

Area of Science:

• Drug Discovery and Development
• Virology
• Medicinal Chemistry

Background:

• Helicases are crucial viral targets, yet remain largely undrugged.
• Developing novel antiviral therapies necessitates effective helicase inhibitors.
• Existing chemogenomic data for helicases is fragmented and requires integration.

Purpose of the Study:

• To create a comprehensive database of helicase inhibitors for drug development support.
• To identify and validate novel small molecule inhibitors targeting viral helicases.
• To provide a valuable resource for researchers in virology and medicinal chemistry.

Main Methods:

• Integrated and curated chemogenomic data from the ChEMBL database for all helicases.
• Developed the Heli-SMACC (Helicase-targeting SMAll Molecule Compound Collection) database.
• Screened 30 selected compounds for SARS-CoV-2 NSP13 ATPase inhibition.

Main Results:

• The Heli-SMACC database contains 20,432 bioactivity entries for viral, human, and bacterial helicases.
• Twelve of the 30 tested compounds showed significant ATPase inhibition against SARS-CoV-2 NSP13.
• These 12 compounds exhibited consistent dose-response curves, indicating reliable inhibitory activity.

Conclusions:

• Heli-SMACC is a valuable, curated resource for advancing helicase inhibitor research.
• The study identified promising lead compounds for the development of new antiviral drugs targeting helicases.
• The database and identified inhibitors can accelerate the discovery of novel therapeutics against viral infections.