Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro

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, re...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Yuyong, Gammeltoft, Karen A., Galli, Andrea, Offersgaard, Anna, Fahnøe, Ulrik, Ramirez, Santseharay, Bukh, Jens, Gottwein, Judith M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537953/
https://www.ncbi.nlm.nih.gov/pubmed/34696509
http://dx.doi.org/10.3390/v13102082
_version_ 1784588391567851520
author Zhou, Yuyong
Gammeltoft, Karen A.
Galli, Andrea
Offersgaard, Anna
Fahnøe, Ulrik
Ramirez, Santseharay
Bukh, Jens
Gottwein, Judith M.
author_facet Zhou, Yuyong
Gammeltoft, Karen A.
Galli, Andrea
Offersgaard, Anna
Fahnøe, Ulrik
Ramirez, Santseharay
Bukh, Jens
Gottwein, Judith M.
author_sort Zhou, Yuyong
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8537953
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85379532021-10-24 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. Viruses Brief Report 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. MDPI 2021-10-15 /pmc/articles/PMC8537953/ /pubmed/34696509 http://dx.doi.org/10.3390/v13102082 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Zhou, Yuyong
Gammeltoft, Karen A.
Galli, Andrea
Offersgaard, Anna
Fahnøe, Ulrik
Ramirez, Santseharay
Bukh, Jens
Gottwein, Judith M.
Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title_full Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title_fullStr Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title_full_unstemmed Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title_short Efficacy of Ion-Channel Inhibitors Amantadine, Memantine and Rimantadine for the Treatment of SARS-CoV-2 In Vitro
title_sort efficacy of ion-channel inhibitors amantadine, memantine and rimantadine for the treatment of sars-cov-2 in vitro
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537953/
https://www.ncbi.nlm.nih.gov/pubmed/34696509
http://dx.doi.org/10.3390/v13102082
work_keys_str_mv AT zhouyuyong efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT gammeltoftkarena efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT galliandrea efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT offersgaardanna efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT fahnøeulrik efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT ramirezsantseharay efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT bukhjens efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro
AT gottweinjudithm efficacyofionchannelinhibitorsamantadinememantineandrimantadineforthetreatmentofsarscov2invitro

Ejemplares similares