High Throughput Screening Assay for Novel HIV Treatment Drugs
Available for Licensing
US Utility Patent Pending (Not Yet Published)
At A Glance
- This cell-based phenotypic assay allows for screening of drugs suppressing HIV-1 protease autoprocessing, an essential step in HIV maturation, thereby inhibiting viral progression
- Currently, most HIV protease inhibitors (PIs) directly target the active site of the mature protease (the product of the autoprocessing reaction), with which drug resistance is often observed in patients under combinational antiretroviral therapy (cART). This invention allows for screening drugs that enable a new cocktail strategy acting on the same target (HIV-1 protease) but at different functional states (precursor and mature PR) and at different regions (non-catalytic and catalytic sites). This approach is expected to drastically suppress emergence of drug-resistance strains and to improve therapy outcomes, thereby preventing HIV resistance
- With roughly 39,000 new cases of HIV per year in the United States alone, there is a clear need for novel drugs that prevent HIV drug resistance long-term
HIV infects roughly 1.1 million Americans in total, with roughly 39,000 new cases per year. These individuals are currently treated with drugs that directly target the viral encoded enzymes essential to viral replication. However, these drugs cannot 100% suppress HIV replication; low levels of viral replication can lead to accumulation of changes (mutations) in the targets rendering resistance to drug treatment. With these ongoing concerns, novel therapeutic drugs with the modes of action different for the currently available anti-HIV medicine are needed.
Inventors at CSU have recently developed a novel screening method for the discovery of drugs selectively suppressing HIV-1 protease autoprocessing. This method uses mammalian cells expressing engineered precursors competent at autoprocessing with a clear readout of how efficient the autoprocessing reaction occurred in transfected cells. Using this platform, drugs can be identified in a high-throughput manner to screen a broad spectrum of potential inhibitors.
- Assay allows for identification of drugs selectively targeting HIV-1 protease autoprocessing, a temporospatially regulated process essential for HIV maturation
- Can rapidly screen many potential HIV inhibitors against variants derived from patients experiencing drug resistance
- These drugs will help to combat HIV developed resistance when used in combination with current drugs on the market
Huang, L., Li, L., Tien, C. et al.Targeting HIV-1 Protease Autoprocessing for High-throughput Drug Discovery and Drug Resistance Assessment. Sci Rep 9, 301 (2019) doi:10.1038/s41598-018-36730-4