Adhirons are efficient tools to guide antiviral ligand discovery

Area of Science:

• Biochemistry
• Drug Discovery
• Virology

Background:

• Adhirons are bacterial antibody-like proteins with high target affinity, useful in research.
• Therapeutic applications of Adhirons are limited, driving the need for alternative strategies.
• Small molecules mimicking Adhiron function are of significant interest for therapeutic development.

Purpose of the Study:

• To develop a novel pipeline for small molecule discovery using Adhirons as templates.
• To accelerate the identification of viral inhibitors through a ligand-based virtual screening workflow.
• To demonstrate the proof of concept using Adhirons against Crimean-Congo Haemorrhagic Fever Virus and Influenza A Virus.

Main Methods:

• Utilized Adhirons as starting templates in a ligand-based virtual screening workflow.
• Employed biophysical and cell-based assays to validate identified small molecule mimics.
• Combined Adhiron data with commercial libraries and structural approaches for inhibitor discovery.

Main Results:

• Successfully identified small molecule mimics with potential inhibitory activity against target viruses.
• Demonstrated the efficacy of the developed pipeline in identifying hits for viral systems.
• Validated the use of Adhirons in accelerating small molecule inhibitor discovery.

Conclusions:

• The developed pipeline effectively uses Adhirons to accelerate small molecule inhibitor discovery for viruses.
• Combining Adhirons, commercial libraries, and structural methods is a viable strategy for drug development.
• This approach holds promise for identifying novel therapeutics against viral infections.