Dipyridamole as a new drug to prevent Epstein-Barr virus reactivation

Antiviral Res. 2019 Dec:172:104615. doi: 10.1016/j.antiviral.2019.104615. Epub 2019 Sep 30.

Abstract

Epstein-Barr virus (EBV) is a widely distributed gamma-herpesvirus that has been associated with various cancers mainly from lymphocytic and epithelial origin. Although EBV-mediated oncogenesis has been associated with viral oncogenes expressed during latency, a growing set of evidence suggested that antiviral treatments directed against EBV lytic phase may contribute to prevent some forms of cancers, including EBV-positive Post-Transplant Lymphoproliferative Diseases. It is shown here that dipyridamole (DIP), a safe drug with favorable and broad pharmacological properties, inhibits EBV reactivation from B-cell lines. DIP repressed immediate early and early genes expression mostly through its ability to inhibit nucleoside uptake. Considering its wide clinical use, DIP repurposing could shortly be evaluated, alone or in combination with other antivirals, to treat EBV-related diseases where lytic replication plays a deleterious role.

Keywords: Dipyridamole; Drug repurposing; EBV reactivation; Epstein-barr virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • Cell Line
  • DNA, Viral / drug effects
  • Dipyridamole / pharmacology*
  • Drug Repositioning
  • Epstein-Barr Virus Infections / drug therapy
  • Gene Expression / drug effects
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism
  • Humans
  • Nucleosides / metabolism
  • Virus Activation / drug effects*
  • Virus Latency / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • DNA, Viral
  • Nucleosides
  • Dipyridamole