SARS-CoV-2 E protein is a potential ion channel that can be inhibited by Gliclazide and Memantine

Biochem Biophys Res Commun. 2020 Sep 10;530(1):10-14. doi: 10.1016/j.bbrc.2020.05.206. Epub 2020 Jun 20.


COVID-19 is one of the most impactful pandemics in recorded history. As such, the identification of inhibitory drugs against its etiological agent, SARS-CoV-2, is of utmost importance, and in particular, repurposing may provide the fastest route to curb the disease. As the first step in this route, we sought to identify an attractive and viable target in the virus for pharmaceutical inhibition. Using three bacteria-based assays that were tested on known viroporins, we demonstrate that one of its essential components, the E protein, is a potential ion channel and, therefore, is an excellent drug target. Channel activity was demonstrated for E proteins in other coronaviruses, providing further emphasis on the importance of this functionally to the virus' pathogenicity. The results of a screening effort involving a repurposing drug library of ion channel blockers yielded two compounds that inhibit the E protein: Gliclazide and Memantine. In conclusion, as a route to curb viral virulence and abate COVID-19, we point to the E protein of SARS-CoV-2 as an attractive drug target and identify off-label compounds that inhibit it.

Keywords: Anti-virals; Bacterial assays; COVID-19.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / metabolism
  • COVID-19
  • Coronavirus Envelope Proteins
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / virology
  • Drug Discovery
  • Drug Repositioning
  • Gliclazide / pharmacology*
  • Humans
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / metabolism
  • Memantine / pharmacology*
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Viral Envelope Proteins / antagonists & inhibitors*
  • Viral Envelope Proteins / metabolism


  • Antiviral Agents
  • Coronavirus Envelope Proteins
  • Ion Channels
  • Viral Envelope Proteins
  • envelope protein, SARS-CoV-2
  • Gliclazide
  • Memantine