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Principal Investigator: Sara Cherry
Organization: UNIVERSITY OF PENNSYLVANIA
Fiscal Year: 2021
Award: $224,752
Funding agency: National Institute of Allergy and Infectious Diseases
Summary
The current outbreak of the coronavirus in China (SARS-CoV-2) has spread rapidly. There are experimental drugs
which will be tested; however, there are no approved therapeutics or vaccines. Indeed, there are tests underway to
determine whether remdesivir, which was developed against filoviruses, can be repurposed against SARS-CoV-2
infection. It would be transformative if we could identify additional small molecules that could be repurposed to treat
the outbreak of SARS-CoV-2 infection. Given that the goal of the parent grant (R01AI150246) is to discover
antivirals active against bunyaviruses, based on findings from cell based screening, and that we have broad
expertise in diverse viruses, we are applying for Supplemental funding (notice number NOT-AI-20-030, PA-18-035)
to expand the scope of the existing grant to use the same methods (small molecule screening) to identify antiviral
therapeutics active against SARS-CoV-2 infection. We will screen two libraries of known bioactives to potentially
repurpose existing therapeutics. First, we will test a library of innate immune agonists (~100 PAMPs) for their ability
to block SARS-CoV-2 infection in human cells including airway cells. Second, we will screen another ‘actionable’
library that I have created as the Director of the High-throughput Screening core at UPENN. We created a library of
~3000 drugs that includes ~1500 FDA approved compounds, ~1000 drugs in clinical trials and the remaining drugs
have known targets. This library has been used for repurposing (as is being done with the Gilead drug remdesivir
that was originally developed against filoviruses) to more rapidly identify active therapeutics for future testing in
humans. We will also determine if any of our active antivirals act synergistically with remdesivir since this drug is
currently under development for use against COVID-19. We expect to identify additional drugs with activity against
SARS-CoV-2.
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