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.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, Antiviral, Remdesivir, ion-channel inhibitor, hepatitis C virus p7 inhibitor, adamantane, combination treatment, barrier to escape, 【초록키워드】 Treatment, Efficacy, coronavirus, Remdesivir, in vitro, severe acute respiratory syndrome Coronavirus, inhibitors, viral entry, Viral, cells, amantadine, respiratory, inhibitor, followed by, selectivity index, Rimantadine, Memantine, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, viral escape, VeroE6 cells, hepatoma, lung carcinoma, effective, highest, antagonistic, Huh7.5,