# Discovery of SARS-CoV-2 antivirals using a replicon assay

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $657,615

## Abstract

PROJECT SUMMARY
 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.

## Key facts

- **NIH application ID:** 10522048
- **Project number:** 1R01AI167356-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Stefan G Sarafianos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $657,615
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522048

## Citation

> US National Institutes of Health, RePORTER application 10522048, Discovery of SARS-CoV-2 antivirals using a replicon assay (1R01AI167356-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10522048. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*