Efficacy of ion-channel inhibitors amantadine, memantine and rimantadine for the treatment of SARS-CoV-2 in vitro
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Efficacy of ion-channel inhibitors amantadine, memantine and rimantadine for the treatment of SARS-CoV-2 in vitro. / Zhou, Yuyong; Gammeltoft, Karen A.; Galli, Andrea; Offersgaard, Anna; Fahnøe, Ulrik; Ramirez, Santseharay; Bukh, Jens; Gottwein, Judith M.
I: Viruses, Bind 13, Nr. 10, 2082, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Efficacy of ion-channel inhibitors amantadine, memantine and rimantadine for the treatment of SARS-CoV-2 in vitro
AU - Zhou, Yuyong
AU - Gammeltoft, Karen A.
AU - Galli, Andrea
AU - Offersgaard, Anna
AU - Fahnøe, Ulrik
AU - Ramirez, Santseharay
AU - Bukh, Jens
AU - Gottwein, Judith M.
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Adamantane
KW - Antiviral
KW - Barrier to escape
KW - Combination treatment
KW - COVID-19
KW - Drug repurposing
KW - Hepatitis C virus p7 inhibitor
KW - Ion-channel inhibitor
KW - Remdesivir
KW - SARS-CoV-2
U2 - 10.3390/v13102082
DO - 10.3390/v13102082
M3 - Journal article
C2 - 34696509
AN - SCOPUS:85117348179
VL - 13
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 10
M1 - 2082
ER -
ID: 283131651