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  • Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2 #MMPMID34853399
  • Toft-Bertelsen TL; Jeppesen MG; Tzortzini E; Xue K; Giller K; Becker S; Mujezinovic A; Bentzen BH; B Andreas L; Kolocouris A; Kledal TN; Rosenkilde MM
  • Commun Biol 2021[Dec]; 4 (1): 1347 PMID34853399show ga
  • 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.
  • |Amantadine/*pharmacology[MESH]
  • |Amiloride/*analogs & derivatives/pharmacology[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Ion Channels/physiology[MESH]
  • |Rimantadine/*pharmacology[MESH]
  • |SARS-CoV-2/*drug effects[MESH]
  • |Viral Proteins/*physiology[MESH]

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  • suck abstract from ncbi

    1347 1.4 2021