Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2

Commun Biol. 2021 Dec 1;4(1):1347. doi: 10.1038/s42003-021-02866-9.


The dire need for COVID-19 treatments has inspired strategies of repurposing approved drugs. Amantadine has been suggested as a candidate, and cellular as well as clinical studies have indicated beneficial effects of this drug. We demonstrate that amantadine and hexamethylene-amiloride (HMA), but not rimantadine, block the ion channel activity of Protein E from SARS-CoV-2, a conserved viroporin among coronaviruses. These findings agree with their binding to Protein E as evaluated by solution NMR and molecular dynamics simulations. Moreover, we identify two novel viroporins of SARS-CoV-2; ORF7b and ORF10, by showing ion channel activity in a X. laevis oocyte expression system. Notably, amantadine also blocks the ion channel activity of ORF10, thereby providing two ion channel targets in SARS-CoV-2 for amantadine treatment in COVID-19 patients. A screen of known viroporin inhibitors on Protein E, ORF7b, ORF10 and Protein 3a from SARS-CoV-2 revealed inhibition of Protein E and ORF7b by emodin and xanthene, the latter also blocking Protein 3a. This illustrates a general potential of well-known ion channel blockers against SARS-CoV-2 and specifically a dual molecular basis for the promising effects of amantadine in COVID-19 treatment. We therefore propose amantadine as a novel, cheap, readily available and effective way to treat COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / pharmacology*
  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Antiviral Agents / pharmacology*
  • Ion Channels / physiology
  • Rimantadine / pharmacology*
  • SARS-CoV-2 / drug effects*
  • Viral Proteins / physiology*


  • Antiviral Agents
  • Ion Channels
  • Viral Proteins
  • Rimantadine
  • 5-(N,N-hexamethylene)amiloride
  • Amiloride
  • Amantadine