Human Immunodeficiency Virus (HIV) creates an incurable infection that uses the replication mechanisms of the host against itself. There are compounds used to treat HIV, but the host is often adversely affected by the treatment. Reverse transcriptase, the enzyme responsible for viral genome duplication, experiences a high degree of mutation and this has been responsible for the slow progression of HIV antiviral treatment. This high degree of mutation leads to a high error load that this study hopes to manipulate and use against the virus. We are developing cytosine-based nucleosides that we hypothesize will undergo tautomerization and consequently, scramble their hydrogen bonding faces thus creating greater mispairing. As it is hypothesized that the HIV genome operates near an “error threshold”, introduction of the tautomer with ambiguous hydrogen bonding into the replication process will lead to an “error catastrophe” and destabilize the replicated duplex thus jettisoning virally infected cells. Design and synthesis of the bicyclic cytosine analogs will be discussed in addition to preliminary work on the spectroscopy of the compounds and oligonucleotide integration.

Ambiguous nucleosides that heighten the HIV error load: Using viral mutagenesis to develop antiviral agents

2019 Spring National Meeting

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