Category: Assay Development and Screening

1183-D - Functional Label-Free Assays to Characterize the In-Vitro Mechanism of Action of Small Molecule Modulators of Capsid Assembly

Tuesday, February 6, 2018
1:00 AM - 6:00 PM

HIV capsid protein is an important target for antiviral drug design. High throughput screening (HTS) campaigns have identified two classes of compounds (PF74 and BI64) that directly target HIV capsid resulting in antiviral activity against HIV-1 and HIV-2 laboratory strains. Using recombinant proteins, we developed a suite of label-free assays to mechanistically understand how these compounds modulate capsid activity. PF74 preferentially binds to the pre-assembled hexameric capsid form and prevents disruption of higher ordered capsid structures by stabilizing capsid inter-subunit interactions. BI64 binds only the monomeric capsid and locks the protein in the assembly incompetent monomeric form by disrupting capsid inter-subunit interactions. These label-free assays could facilitate the identification of a different class of small molecule modulators of capsid function.

Sheila Clancy

Associate Scientist 2
Gilead Sciences
Foster City, CA

High throughput biology