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Updated: Aug 29, 2025

High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
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High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions

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Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants

Jing Xing1, Rama Shankar1, Meehyun Ko2

  • 1Department of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI 49503, USA.

Iscience
|September 12, 2022
PubMed

Insights

Researchers identified a drug, IMD-0354, that reverses host gene expression changes caused by SARS-CoV-2 infection and its variants. This approach aids in discovering new antiviral therapies for evolving coronaviruses.

Area of Science:

  • Virology
  • Genomics
  • Pharmacology

Background:

  • Host cell responses to SARS-CoV-2 and its variants vary significantly, complicating host-based antiviral drug discovery.
  • Antiviral drugs are hypothesized to counteract viral infection by reversing global host gene expression patterns.

Purpose of the Study:

  • To identify host transcriptomic signatures of coronavirus infection and evaluate their potential for therapeutic discovery.
  • To discover novel antiviral compounds effective against SARS-CoV-2 and its variants using a transcriptomic reversal approach.

Main Methods:

  • Retrospective analysis of 1,700 host transcriptomic profiles from SARS, MERS, and SARS-CoV-2 infections.
  • Iterative, data-driven evaluation of gene expression signatures to identify those reversible by antiviral agents.
  • In vitro testing of candidate compounds, including IMD-0354, against SARS-CoV-2 and its variants.

Main Results:

  • Identified conserved coronavirus infection signatures across different host models and conditions.
  • Discovered IMD-0354, a compound that globally reverses host gene expression signatures with nanomolar IC50 values against SARS-CoV-2 and five variants.
  • IMD-0354 demonstrated antiviral activity by stimulating type I interferon response, inhibiting viral entry, and reducing viral protein hijacking.

Conclusions:

  • The transcriptomic reversal approach, leveraging conserved coronavirus signatures and polypharmacology, is a viable strategy for discovering new antiviral therapeutics.
  • IMD-0354 shows significant promise as a broad-spectrum antiviral agent against SARS-CoV-2 and its evolving variants.
Keywords:
BioinformaticsMicrobiologyOmicsTranscriptomicsVirology

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