Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro.
A549 Cells
Adenosine Monophosphate
/ analogs & derivatives
Alanine
/ analogs & derivatives
Amantadine
/ pharmacology
Animals
Antiviral Agents
/ pharmacology
Cell Line, Tumor
Chlorocebus aethiops
Denmark
Drug Repositioning
Humans
Ion Channels
/ antagonists & inhibitors
Memantine
/ pharmacology
Rimantadine
/ pharmacology
SARS-CoV-2
/ drug effects
Vero Cells
COVID-19 Drug Treatment
COVID-19
SARS-CoV-2
adamantane
antiviral
barrier to escape
combination treatment
drug repurposing
hepatitis C virus p7 inhibitor
ion-channel inhibitor
remdesivir
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
received:
31
08
2021
revised:
24
09
2021
accepted:
05
10
2021
entrez:
26
10
2021
pubmed:
27
10
2021
medline:
11
11
2021
Statut:
epublish
Résumé
We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine also showed the highest selectivity index, followed by amantadine and memantine (17.3, 12.2 and 7.6, respectively). Similar results were observed in human hepatoma Huh7.5 and lung carcinoma A549-hACE2 cells. Inhibitors interacted in a similar antagonistic manner with remdesivir and had a similar barrier to viral escape. Rimantadine acted mainly at the viral post-entry level and partially at the viral entry level. Based on these results, rimantadine showed the most promise for treatment of SARS-CoV-2.
Identifiants
pubmed: 34696509
pii: v13102082
doi: 10.3390/v13102082
pmc: PMC8537953
pii:
doi:
Substances chimiques
Antiviral Agents
0
Ion Channels
0
Rimantadine
0T2EF4JQTU
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Amantadine
BF4C9Z1J53
Alanine
OF5P57N2ZX
Memantine
W8O17SJF3T
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : China Scholarship Council
ID : CSC NO. 201806910045
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