RNA-Targeted Small Molecules as Potential Antiviral Therapy (HIV, SARS etc)
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A high error rate of HIV -I reverse transcriptase coupled with a fast replication
cycle associated with HIV -1 favors rapid development and selection of drug resistant strains. Therefore, identification of small molecules capable of inhibiting viral components necessary for HIV -1 proliferation continues to be of great importance. The full length HIV mRNA encodes two polyprotein precursors, Gag and Pol. While derived from the same mRNA, the Pol polyprotein, which is always produced as a Gag-Pol fusion protein, is only translated 5-10% of the time. This efficiency has been found to be critically important for HIV -1 replication, as either an increase or decrease in Gag-Pol results in a significant reduction of virus particles produced. Synthesis of the Gag-Pol fusion protein is brought about by a programmed ribosomal frameshift. Two RNA elements have been reported to be essential for this frameshift.
The small molecules found by the inventors target frameshift sequences in RNA, a recognized goal in anti-HIV research.These findings will be applicable in the development of antiviral therapies for the treatment of HIV, SARS etc.
The researchers have identified selective nucleic acid binding compounds that are directed at RNA targets involved in the stem/loop frameshift site associated with Gag/Pol expression of HIV. These compounds have demonstrated success in inhibiting the activity of the target nucleic acid molecules and bind selectively to the HIV-1 frameshift regulatory sequence. These compounds are potential inhibitors of HIV-1 replication. These compounds can be used in combination with other known or hereafter developed therapies for HIV infection.
Nucleic Acid Binding Compounds and Methods of Use
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