@article{3033232,
    title = "Amantadine has potential for the treatment of COVID-19 because it
inhibits known and novel ion channels encoded by SARS-CoV-2",
    author = "Toft-Bertelsen, Trine Lisberg and Jeppesen, Mads Gravers and Tzortzini, and Eva and Xue, Kai and Giller, Karin and Becker, Stefan and Mujezinovic, and Amer and Bentzen, Bo Hjorth and Andreas, Loren B. and Kolocouris, and Antonios and Kledal, Thomas Nitschke and Rosenkilde, Mette Marie",
    journal = "Communicative & Integrative Biology",
    year = "2021",
    volume = "4",
    number = "1",
    publisher = "NATURE PORTFOLIO",
    issn = "1942-0889",
    doi = "10.1038/s42003-021-02866-9",
    abstract = "Toft-Bertelsen et al. describe repurposing of anti-influenza drug
amantadine and its derivatives for the treatment of SARS-CoV-2. They
show that Amantadine, Emodin and Xanthene show significant blockage of
ionchannels formed by SARS-CoV-2 which are crucial for its assembly and
pathophysiology.
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."
}