Viktoriya Anokhina, M.S.
BMB Biochemistry & Molecular Biology Ph.D. Program
Research Interest: Despite the progress in treatment with combination antiretroviral therapy (cART), HIV/AIDS remains one of the world's most significant public health challenges, since there is no complete recovery from the disease. More research is needed to explore new viral targets and develop other therapies. Targeting functionally important RNA elements can potentially provide a new avenue for therapeutic development. In addition, principles learned from the development of molecules targeting HIV-1 RNA elements can be applied to other pathological RNAs. One of the potential targets in HIV-1 is the Frameshifting Stimulatory Signal (FSS), a highly stable RNA hairpin that is essential for precisely regulating the ratio of translation for “structural” and “enzymatic” polyproteins. Misregulation leads to formation of non-infectious viral particles. Thus, it has been hypothesized that targeting HIV-1 FSS could be of therapeutic value.
In the Miller lab, we developed compounds that bind to HIV-1 FSS RNAs with affinities 16-100 nM. Compounds ablate virus production and infectivity in human MT-2T cells infected with laboratory HIVIIIB and with a drug-resistant patient isolate. Several pieces of evidence altogether demonstrate that the antiviral effectivity of compounds is due to compound-mediated interference with ribosomal frameshifting via binding to the HIV-1 FSS. While the binding affinities of these molecules to the HIV-1 FSS lie in the nM range, biological activity in cellular assays is observed at μM range. We hypothesized that this discrepancy is associated with low cellular permeability of the compounds. My efforts are focused on testing methods of improving compounds efficacy by developing new delivery strategies, while maintaining compound selectivity and affinity toward the target. These methods should have general utility for RNA-targeted drugs.