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Updated: Sep 21, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Signaling Pathway Reporter Screen with SARS-CoV-2 Proteins Identifies nsp5 as a Repressor of p53 Activity

Abhishek Kumar1, Tristan R Grams2, David C Bloom2

  • 1Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL 32610, USA.

Viruses
|May 28, 2022
PubMed

Insights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins disrupt host signaling pathways. The p53 protein restricts SARS-CoV-2, but viral protease nsp5 inhibits p53 activity, aiding infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Host signaling pathway dysregulation is crucial in SARS-CoV-2 infection and pathogenesis.
  • While some viral proteins blocking type I IFN signaling are known, a comprehensive analysis of SARS-CoV-2 proteins affecting other critical pathways is missing.

Purpose of the Study:

  • To screen the impact of 21 SARS-CoV-2 proteins on 10 key host signaling pathways.
  • To identify SARS-CoV-2 proteins that modulate host signaling pathways.
  • To investigate the role of p53 as a host restriction factor against SARS-CoV-2.

Main Methods:

  • Utilized a luciferase reporter assay to screen 21 SARS-CoV-2 proteins.
  • Assessed the effects on 10 host signaling pathways: Wnt, p53, TGFβ, c-Myc, Hypoxia, Hippo, AP-1, Notch, Oct4/Sox2, and NF-κB.
  • Performed overexpression studies in HEK293T cells.

Main Results:

  • Identified SARS-CoV-2 proteins acting as activators or inhibitors of specific host signaling pathways.
  • Demonstrated that p53 acts as an intrinsic host restriction factor, reducing SARS-CoV-2 production when overexpressed.
  • Showed that the SARS-CoV-2 main protease (nsp5) represses p53 transcriptional activity in a protease-dependent manner.

Conclusions:

  • SARS-CoV-2 proteins significantly regulate host signaling pathways, influencing viral infection and pathogenesis.
  • p53 is a critical host defense mechanism against SARS-CoV-2, targeted by the viral protease nsp5.
  • Findings provide a basis for understanding how SARS-CoV-2 manipulates host pathways to control infection.
Keywords:
COVID-19SARS-CoV-2coronavirusnsp5p53signaling pathway

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