Trana Discovery's HIV Assay Finds Compounds that Inhibit NNRTI and Multi-Drug Resistant HIV Viruses

CARY, NC (December 14, 2010) – Trana Discovery, Inc., an infectious disease drug discovery technology company, today announced that a recent study sponsored by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health, affirms that bioactive compounds selected using the Trana HIV 201 High-Throughput (HTS) Assay inhibit viral strains demonstrating resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). The results of the in vitro testing indicate that the selected compounds do not appear to act as NNRTIs, but rather by a different mechanism of action. In addition, these compounds were found to modestly inhibit a multi-drug resistant virus that has demonstrated resistance to commonly prescribed HIV treatments such as nevirapine, saquinavir, 3TC and AZT.

The Trana HIV assay is based on the premise that HIV has evolved to use tRNALys3 as a primer for initiation of reverse transcription. The tRNALys3 primer is required to copy its genetic material and generate new viruses. Therefore, the interaction between tRNALys3 and viral genomic RNA represents a potential novel target for HIV drug development. The Trana HIV assay is designed to select compounds that inhibit the use of tRNALys3 by HIV and that in turn can be developed as new anti-HIV drug therapies.

Through a collaboration with Southern Research Institute, the HIV assay was deployed in three separate screening campaigns against more than 120,000 diverse compounds. Seven bioactive compounds were selected for additional follow-up testing and characterization in dose-response against NNRTI-resistant HIV isolates in peripheral blood mononuclear cell (PBMC) assays. These seven compounds were previously found to have modest antiviral activity against HIV in a cell-based assay.

Testing against NNRTI-resistant viruses was conducted to study whether or not the compounds were acting as NNRTIs. The results from this testing indicated there was no apparent difference in antiviral activity based on the presence of NNRTI-resistance mutations in the viruses, which indicates the compounds don’t appear to act as NNRTIs.

"These results help to demonstrate that the Trana HIV assay identifies compounds that act through a different mechanism of action,” said Steve Peterson, CEO of Trana Discovery. “Trana has filed for patent protection on these compounds as well as their ability to inhibit HIV-resistant isolates. We are now in a position to license the HIV assay, drug class and bioactive compounds to qualified pharmaceutical companies for further development."

High-throughput screening of an additional 200,000 compounds using the Trana HIV 201 HTS Assay has recently been completed. Compounds found to be active as a result of this additional screening are currently being identified for similar follow-up testing against HIV replication in cell-based assays. Based on prior experience, similar results are anticipated.

High-throughput screening using the Trana HIV 201 HTS Assay and follow-up testing of compounds for bioactivity against HIV in cell-based assays was performed under the NIAID, DAIDS contract N01-AI-70042; Roger Miller, Project Officer. In addition, testing of the compounds against NNRTI and multi-drug resistant HIV in PBMCs was supported by the NIAID, DAIDS contract N01-AI-70041; Steven Turk, Project Officer.

Click to view a video on the Trana HIV 201 HTS Assay and how it works.

The Trana HIV 201 HTS Assay can be used to search company-owned compound libraries, confirm the mechanism of action for black-hole leads, or screen other commercially available compound libraries. Organizations interested in licensing the assay, class and bioactive compounds should contact Trana at info@tranadiscovery.com or by calling 866-390-3452 (toll free) or +1-919-342-6192.

About Trana Discovery, Inc.

Trana Discovery, an anti-infective drug discovery technology company, helps its partners find new classes of drugs for the treatment of serious bacterial, viral, and fungal infectious diseases. Our proprietary assays identify compounds that work through a unique mechanism of action: inhibition of the target pathogen's ability to use transfer RNA (tRNA) essential for propagation. The use of high-throughput screening assays developed by Trana Discovery will reduce the cost and time for drug discovery. Our assays provide licensing opportunities for exclusive rights to new drug classes. Trana Discovery has licensed the patented technology emanating from 20 years of research conducted at North Carolina State University, and holds patents that expand on this core technology and its use in high throughput screening. The company is located in Cary, North Carolina. For more information, please visit www.tranadiscovery.com.

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