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

Abstract

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.

Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system

“…VeroE6 cells (gift from J. Dubuisson) were cultured in Dulbecco’s modified Eagle’s medium (Invitrogen, Paisley, UK) as described ( 15 , 26 , 27 ). A549-hACE2 cells (InvivoGen, Toulouse, France) were cultured in Dulbecco’s modified Eagle’s medium: Nutrient Mixture F-12 (Gibco, Paisley, UK) as described ( 15 , 26 , 27 ).…”

“…VeroE6 cells (gift from J. Dubuisson) were cultured in Dulbecco’s modified Eagle’s medium (Invitrogen, Paisley, UK) as described ( 15 , 26 , 27 ). A549-hACE2 cells (InvivoGen, Toulouse, France) were cultured in Dulbecco’s modified Eagle’s medium: Nutrient Mixture F-12 (Gibco, Paisley, UK) as described ( 15 , 26 , 27 ). Both culture media were supplemented with 10% heat-inactivated fetal bovine serum (Sigma-Aldrich, St. Louis, MO, USA), penicillin (100 U/ml), and streptomycin (100 μg/ml; Gibco/Invitrogen Corporation, Carlsbad, CA, USA).…”

A Hydrazine–Hydrazone Adamantine Compound Shows Antimycobacterial Activity and Is a Probable Inhibitor of MmpL3

“…The adamantane molecule consists of three connected cyclohexane rings. Adamantane derivatives, such as amantadine, have been found to have antiviral activity [ 16 ]. Adamantylureas, such as AU1235 [ 17 ] and SQ109 [ 18 ], were previously identified as a group of compounds that are active against M. tuberculosisi as potential inhibitors of MmpL3.…”

Polysaccharides and Their Derivatives as Potential Antiviral Molecules

“…Antiviral drugs may have an inhibitory effect on the entire replication cycle. They can be classified according to the stage to which they are targeted: cell entry inhibitors [52][53][54][55][56][57], replicant inhibitors [40,[58][59][60][61][62][63][64] and assembly, maturation, and release inhibitors [65][66][67][68][69]. Within a therapeutic class, antiviral agents can have different effects.…”