Network Controllability-Based Prioritization of Candidates for SARS-CoV-2 Drug Repositioning

Viruses. 2020 Sep 26;12(10):1087. doi: 10.3390/v12101087.

Abstract

In a short time, the COVID-19 pandemic has left the world with over 25 million cases and staggering death tolls that are still rising. Treatments for SARS-CoV-2 infection are desperately needed as there are currently no approved drug therapies. With limited knowledge of viral mechanisms, a network controllability method of prioritizing existing drugs for repurposing efforts is optimal for quickly moving through the drug approval pipeline using limited, available, virus-specific data. Based on network topology and controllability, 16 proteins involved in translation, cellular transport, cellular stress, and host immune response are predicted as regulators of the SARS-CoV-2 infected cell. Of the 16, eight are prioritized as possible drug targets where two, PVR and SCARB1, are previously unexplored. Known compounds targeting these genes are suggested for viral inhibition study. Prioritized proteins in agreement with previous analysis and viral inhibition studies verify the ability of network controllability to predict biologically relevant candidates.

Keywords: COVID-19; SARS-CoV-2; drug repositioning; network biology; virus-host interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / drug effects*
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / physiology
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Drug Approval
  • Drug Delivery Systems
  • Drug Repositioning / methods*
  • Host-Pathogen Interactions
  • Humans
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Protein Interaction Maps / drug effects
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Scavenger Receptors, Class B / metabolism
  • Virus Integration

Substances

  • Receptors, Virus
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • poliovirus receptor