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.

Public Health Relevance

Due to the dearth of antiviral therapeutics, there is an urgent need for the discovery of novel therapeutics active against emerging viruses, with this supplement focusing on SARS-CoV-2. There are no approved treatments and thus we will screen a library of approved drugs to potentially repurpose existing therapeutics for use against this emerging pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI150246-01S1
Application #
10126644
Study Section
Program Officer
Alarcon, Rodolfo M
Project Start
2020-05-18
Project End
2022-08-31
Budget Start
2020-05-18
Budget End
2020-08-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104