Brief Description:
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.
Applications:
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.
Advantages:
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.