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Scripps Maps Human Proteins SARS-CoV-2 Exploits, Identifying Drug Targets With Preclinical Support

The peer-reviewed work spotlights host pathways the virus relies on, suggesting routes to pan-coronavirus treatments less prone to resistance.

Overview

  • A genome-wide siRNA screen in susceptible human cells cataloged 32 proteins needed early in infection and 27 used in later stages of the SARS-CoV-2 life cycle.
  • Perlecan emerged as a potential co-receptor, with experiments showing the viral spike protein binds its sugar chains to facilitate cell entry.
  • Targeting BIRC2 with Smac mimetic compounds cut viral levels in a SARS-CoV-2 mouse model and suppressed infection in cell cultures.
  • Cross-testing against SARS-CoV-1, MERS-CoV and a seasonal coronavirus found 17 of 47 host factors were shared, supporting broad-spectrum antiviral prospects.
  • Researchers plan further safety and efficacy studies and will probe whether the same host dependencies apply to other respiratory pathogens such as influenza and RSV.