Discovery of sars-COV-2 antivirals using a replicon assay

Active Project Grant Awarded Last action

Award ID
R01AI167356
Recipient
Awarding agency
Obligated
$6,185,846

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 85% complete
Place of performance
Atlanta, GA 30322, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) cause severe diseases in humans (covid- 19) that presents a major threat for global public health. Since IT was first reported in 12/2019, covid-19 has become a pandemic that continues to spread, with >246 million confirmed cases and >5 million deaths as of 11/02/2021. In addition to the human tragedy, the magnitude of the pandemic-driven implosion of global economies is enormous. Although vaccines are now available, their efficacy appears to be reduced with spreading viral strains. Remdesivir is the only approved antiviral targeting SARS-COV-2, but IT has little effect on covid-19 mortality. Therefore, IT is critical to identify and develop additional antivirals to combat viral infection. The following strong preliminary data enable targeting of SARS-COV-2: 1) construction of an extensive collection of SARS-COV-2 replicon systems that enable cutting-edge, rapid, and economical high-throughput screening. 2) preparation of cell lines that stably express SARS-COV-2 replicon. 3) preliminary screening of chemical libraries led to the discovery of a novel SARS-COV-2 antiviral, which has already been improved with one round of optimization through medicinal chemistry efforts. 4) multiplex visualization of single-genomic or subgenomic (+) or (-) SARS-COV-2 RNA and simultaneously viral and/or host proteins in individual infected cells. 5) cutting-edge rapid high-throughput infectious virus BSL3 assays that enable kinetic, mechanistic, drug resistance studies. 6) in-house cloning expression and purification of 10 SARS-COV-2 non-structural proteins (NSPS). 7) biochemical and biophysical assays to measure the enzymatic activities of several SARS-COV and SARS-COV-2 NSP proteins and to measure compound binding to NSPS. We hypothesize that our recently developed replicon systems can be used for the discovery of anti-SARS- COV-2 hits, which upon HIT-to-lead optimization can become covid-19 drug candidates. To address this hypothesis, we propose the following specific aims: 1. Use of SARS-COV-2 replicon plasmid systems and SARS-COV-2 replicon-expressing cell lines to screen chemical libraries for antiviral hits. 2. Inhibition and resistance studies with prioritized inhibitors. 3. HIT-to-lead optimization these studies will lead to antivirals with strong potency and pharmacokinetic profiles, setting the stage for development of SARS-COV-2 antivirals and combination therapies.

Transactions

Action Obligated Date
Amendment -$695,135
Amendment $695,135
Amendment $695,135
Amendment $0
Amendment $0
Amendment $75,307
Amendment $75,307
Amendment $678,703
Amendment $678,703
Amendment $13,952
Amendment $13,952
Amendment $13,952
Amendment $643,490
Amendment $643,490
Amendment $643,490
Amendment $657,615
Original award $657,615
Show all 17

Subawards

Subrecipient Amount Awarded
Regents Of The University Of Minnesota Discovery of SARS-CoV-2 antivirals using a replicon assay $184,800
Regents Of The University Of Minnesota $186,000
Regents Of The University Of Minnesota $186,000
Regents Of The University Of Minnesota $186,000

Quick answers

Who received award R01AI167356?

R01AI167356 was awarded to Emory University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 1, 2022.

How much is award R01AI167356 worth?

$6,185,846 has been obligated on R01AI167356.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login