Novel Therapeutics Directed to SARS-CoV2 RNA Targets
The COVID-19 outbreak has crystallized the urgent need for therapeutics to inhibit transmission in human populations. Halting viral protein synthesis is fundamental to limiting transmission and pathogenesis.
This study will produce lead compounds that inhibit the synthesis of SARS-CoV2 viral proteins and attenuate SARS-CoV2 transmission.
In this study researchers will:
- Employ FDA-approved compounds and optimized small molecules with affinity and specificity for RNA targets.
- Apply cell-based and future biophysical screening tools to identify molecules with specificity to SARS-CoV2 RNA without cellular toxicity. This research will identify small molecule inhibitors of SARS-CoV2 RNA.
The 5' end of all SARS-CoV2 RNAs is identical and highly conserved. This 65 nucleotide sequence has an integral role in the viral replication cycle.
In preliminary studies, researchers have identified RNA-biased small molecules binding the 5' end of HIV RNA at concentrations within the range of compounds in clinical trials. The effect of these compounds on HIV replication was documented. The compounds reduced virion production and diminished sentinel replication intermediates. Here researchers will employ the validated viral screening assay to identify compounds binding the SARS-CoV2 RNA and deregulating SARS-CoV2 RNA function.
This project is supported by the UMN Campus Public Health Officer's CO:VID (Collaborative Outcomes: Visionary Innovation & Discovery) grants program, which support University of Minnesota faculty to catalyze and energize small-scale research projects designed to address and mitigate the COVID-19 virus and its associated risks.