# Control of Protein Synthesis by the UPS Under Stress

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $87,750

## Abstract

Project Summary
Following its infection, SARS-CoV-2 utilizes cellular networks to enable its efficient replication. Key for its success
in hijacking cellular systems of host cells lies in the takeover of the translational apparatus, whereby the virus
requires eukaryotic translation initiation complex 4F (eIF4F) activity. To this end, cap-dependent and eIF4F-
driven viral genome RNA translation is essential for production of the viral proteins required for its replication.
Notably, cancer cells rewire their RNA translational machinery, as often reflected by enhanced activity and/or
expression of eIF4F subunits leading to increased complex activity. Thus, SARS-CoV-2 and translational
perturbations in cancer may converge on cap-dependent translation and, in particular, on the eIF4F complex.
Accordingly, a different degree of susceptibility to SARS-CoV-2 infection is expected in cancer cells based on
their pre-rewiring of the RNA translation machinery. The underlying hypothesis of this proposal is that targeting
components of the eIF4F complex is expected to provide novel therapeutic modality for inhibition of
SARS-CoV-2 replication, while exerting anti-neoplastic effects across broad spectrum of cancers. To test
this, we will define the effectiveness of RNA translation modulators, we have developed, in attenuating SARS-
CoV-2 effect on eIF4F activity in lung cancer cells susceptible to coronavirus infection. The effect of RNA
translation modulators on SARS-CoV-2 infected lung cancer cells response to commonly used therapy will be
also assessed. This is anticipated to improve understanding of coronavirus biology in context of neoplasia and
in long-term provide therapeutic modalities for cancer patients infected with SARS-CoV-2 or other coronaviruses
anticipated to cause future pandemics.

## Key facts

- **NIH application ID:** 10146220
- **Project number:** 3R01CA202021-05S1
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Zeev A. Ronai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $87,750
- **Award type:** 3
- **Project period:** 2016-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146220

## Citation

> US National Institutes of Health, RePORTER application 10146220, Control of Protein Synthesis by the UPS Under Stress (3R01CA202021-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146220. Licensed CC0.

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