# Overriding the Immune Evasion Tactics of Coronavirus

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $617,996

## Abstract

PROJECT SUMMARY/ABSTRACT
Progression of SARS-Coronavirus-2 (SARS-CoV-2) infected patients to life threatening disease may result from
a virus-mediated, dysregulated immune response associated with excessive production of inflammatory
cytokines, cytokine release syndrome. In this proposal we seek to identify therapeutics and knowledge of
Coronaviruses that will counteract the disruption in cytokine signaling pathways involved in effective host
defense.
 We contribute to the urgent need for therapeutics that inhibit SARS-CoV-2 infection using pathway
specific reporter cells to screen for therapeutically active compounds that restore cytokine signaling. Our pathway
specific screens are a component in SBP-wide initiative to develop therapeutics that limit severe COVID-19. Our
screening strategy selects drugs identified in libraries of pharmacologically active therapeutics that block SARS-
CoV-2 lytic replication. We use cytokine pathway reporters to test these compounds in SARS-CoV-2 infection of
a lung cell line and human lung organoids in BSL3 facilities. The selected candidates will undergo analysis for
potential drug development.
 Fundamental knowledge of cytokine-regulated defense mechanisms related to Coronavirus infection
limits the rational design of therapeutics and vaccines. To advance this knowledge we focus on the Lymphotoxin-
β Receptor (LTβR) and the Herpesvirus entry mediator (HVEM, TNFRSF14) pathways known to regulate anti-
viral cytokines, interferons (IFN) and interleukin-1(IL1β). Together, the LTβR and HVEM pathways act as an
integrated, homeostatic network that inhibits virus replication yet limits tissue damaging cytokines. Two SARS-
CoV-2 proteins, the Papain-like protease (PLPro, Nsp3) and Nsp9 target novel components in the TRAF3
interactome that control the NFκB transcriptome. We will determine the role of these components in the key
cytokine pathways using genetic and pharmacologic approaches in a mouse coronavirus lung infection model.
Together these two independent but complementary aims will provide an opportunity to help solve the SARS-
CoV-2 pandemic, and protect future generations.

## Key facts

- **NIH application ID:** 10188930
- **Project number:** 1R01AI158552-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Carl F Ware
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $617,996
- **Award type:** 1
- **Project period:** 2020-08-12 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188930

## Citation

> US National Institutes of Health, RePORTER application 10188930, Overriding the Immune Evasion Tactics of Coronavirus (1R01AI158552-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10188930. Licensed CC0.

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