Glibenclamide inhibits BK polyomavirus infection in kidney cells through CFTR blockade

Antiviral Res. 2020 Jun:178:104778. doi: 10.1016/j.antiviral.2020.104778. Epub 2020 Mar 27.


BK polyomavirus (BKPyV) is a ubiquitous pathogen in the human population that is asymptomatic in healthy individuals, but can be life-threatening in those undergoing kidney transplant. To-date, no vaccines or anti-viral therapies are available to treat human BKPyV infections. New therapeutic strategies are urgently required. In this study, using a rational pharmacological screening regimen of known ion channel modulating compounds, we show that BKPyV requires cystic fibrosis transmembrane conductance regulator (CFTR) activity to infect primary renal proximal tubular epithelial cells. Disrupting CFTR function through treatment with the clinically available drug glibenclamide, the CFTR inhibitor CFTR172, or CFTR-silencing, all reduced BKPyV infection. Specifically, time of addition assays and the assessment of the exposure of VP2/VP3 minor capsid proteins indicated a role for CFTR during BKPyV transport to the endoplasmic reticulum, an essential step during the early stages of BKPyV infection. We thus establish CFTR as an important host-factor in the BKPyV life cycle and reveal CFTR modulators as potential anti-BKPyV therapies.

Keywords: BK virus; CFTR; Glibenclamide; Ion channel; PVAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • BK Virus / drug effects*
  • BK Virus / physiology
  • Capsid Proteins / metabolism
  • Cells, Cultured
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Glyburide / pharmacology*
  • Humans
  • KATP Channels / antagonists & inhibitors
  • KATP Channels / metabolism
  • Kidney Tubules, Proximal
  • Potassium Channel Blockers / pharmacology
  • Urothelium / cytology
  • Urothelium / virology
  • Virus Replication


  • Antiviral Agents
  • CFTR protein, human
  • Capsid Proteins
  • KATP Channels
  • Polyomavirus major capsid protein VP1
  • Potassium Channel Blockers
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Glyburide