Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2.
Commun Biol
; 4(1): 1347, 2021 12 01.
Article
in English
| MEDLINE | ID: covidwho-1852515
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Proteins
/
Rimantadine
/
Amantadine
/
Amiloride
/
SARS-CoV-2
Type of study:
Experimental Studies
/
Prognostic study
Language:
English
Journal:
Commun Biol
Year:
2021
Document Type:
Article
Affiliation country:
S42003-021-02866-9
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