Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality

J Cell Biol. 2020 Oct 5;219(10):e202006159. doi: 10.1083/jcb.202006159.


With the rapid global spread of SARS-CoV-2, we have become acutely aware of the inadequacies of our ability to respond to viral epidemics. Although disrupting the viral life cycle is critical for limiting viral spread and disease, it has proven challenging to develop targeted and selective therapeutics. Synthetic lethality offers a promising but largely unexploited strategy against infectious viral disease; as viruses infect cells, they abnormally alter the cell state, unwittingly exposing new vulnerabilities in the infected cell. Therefore, we propose that effective therapies can be developed to selectively target the virally reconfigured host cell networks that accompany altered cellular states to cripple the host cell that has been converted into a virus factory, thus disrupting the viral life cycle.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Drug Discovery
  • Host Microbial Interactions / drug effects*
  • Humans
  • Immunologic Factors / pharmacology
  • Metabolic Networks and Pathways / drug effects
  • Protein Interaction Maps
  • Proteolysis
  • RNA Viruses / drug effects
  • RNA Viruses / physiology
  • Virus Diseases / drug therapy*
  • Virus Diseases / genetics
  • Virus Replication / drug effects*


  • Antiviral Agents
  • Immunologic Factors