Do the hits bind to other tRNAs?
There are two basic reasons as to why we currently believe that our hits do not bind to other tRNAs. First, based on our limited data set these compounds are not indiscriminate toxins; thus, they are most likely not indiscriminate binders to tRNA even though the compounds are active in our assay and inhibit HIV in a PBMC assay. Second, HIV does not recognize normally configured tRNALys3, thus, the site of potential interaction of these compounds with other tRNA is not readily accessible. The normal configuration of the ultra conserved ASL loop of tRNALys3 looks much like the AIDS red ribbon lapel pin. This configuration is different when the HIV viral RNA forms a complex with the tRNALys3. The virus uncoils the “red ribbon” described above into a bimolecular duplex conformation that looks much like a short piece of a double helix.
