Inhibition of Retroelement Replication with Divalent Cations
AIDS is a devastating disease caused by the HIV-1 virus. Happily, there are now highly active antiviral drug cocktails available that allow many patients to control the disease. Nevertheless, many patients continue to have problems because of viral resistance and because of side effects. Thus there is an ongoing need for new pharmaceutical interventions. New drug targets are especially useful as they can increase the potency of multiple drug formulation. We have identified a completely unique molecular target for controlling HIV-1 and in principle other viruses that depend on the enzyme reverse transcriptase such as HTLV-1, which causes adult T cell lymphoma, and the hepatitis B virus. The molecular target identified is an ion exporter called PMR1 which normally pumps Manganese ions out of the cell. Our research shows that elevating intracellular Manganese ion concentrations even modestly has profound effects on the efficiency of reverse transcription, both in the test tube and inside cells. Thus targeting this transporter is likely to have a profound effect on viral multiplication. We have developed an efficient and effective yeast-based screen for identifying chemical compounds that inhibit the human PMR1 protein and have reduced the screen to practice. It currently operates in a 96 well format and can be scaled to screen (conservatively) thousands of compounds a week. We seek partners in the pharmaceutical industry capable of large-scale screening to discover novel anti-HIV-1 drugs. Description (Set) Proposed Use (Set) The screen can be used to identify lead compounds for eventual use as novel anti-retroviral drugs.Inventor(s): Boeke, Jef D.
Type of Offer: Licensing
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