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Related Concept Videos

Human Virome01:26

Human Virome

The human body harbors a vast and diverse viral community known as the human virome. The virome includes bacteriophages that infect bacteria, and eukaryotic viruses that infect human cells. Transient dietary and environmental viruses also contribute to this dynamic ecosystem. Estimates suggest the human body may contain on the order of 10¹³ viral particles, though abundance varies widely by body site and detection method.Comprehensive characterization of the virome has become possible only with...
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Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...

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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
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Predicting host-based, synthetic lethal antiviral targets from omics data.

Jeannette P Staheli1, Maxwell L Neal1, Arti Navare1

  • 1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.

NAR Molecular Medicine
|July 12, 2024
PubMed
Summary
This summary is machine-generated.

This study identifies novel host-based antiviral targets by analyzing synthetic lethal (SL) interactions. Gene depletion data from CRISPR knockout (KO) screens reveal potential broad-spectrum drug targets for viral infections like SARS-CoV-2 and influenza.

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Area of Science:

  • Virology
  • Genetics
  • Drug Discovery

Background:

  • Traditional antiviral therapies face challenges with toxicity and drug resistance.
  • Host-based antivirals offer an alternative but can have nonspecific effects.
  • Targeting synthetic lethal (SL) partners of virus-disrupted proteins enables selective elimination of infected cells.

Purpose of the Study:

  • To hypothesize and computationally predict antiviral drug targets based on synthetic lethal (SL) interactions.
  • To investigate if genes depleted in CRISPR knockout (KO) screens of virus-infected cells are enriched in SL partners of infection-altered proteins.
  • To identify broad-spectrum, host-based antiviral SL targets.

Main Methods:

  • Established a computational pipeline for predicting antiviral SL drug targets.
  • Identified SARS-CoV-2-induced gene product alterations using omics data.
  • Determined SL partners for each altered gene product.
  • Screened CRISPR KO data for SL partners essential for infected cell viability.

Main Results:

  • Despite variations in omics data, common predicted SL targets were identified.
  • Significant enrichment of SL targets was found in CRISPR KO-depleted datasets.
  • Comparison of SARS-CoV-2 and influenza data revealed shared potential broad-spectrum antiviral SL targets.

Conclusions:

  • CRISPR KO data contain common antiviral targets due to their SL relationship with virus-altered states.
  • Analysis of omics data and SL predictions can reveal these broad-spectrum antiviral targets.
  • This approach offers a promising strategy for developing novel host-based antiviral therapies.