Amantadine Inhibits SARS-CoV-2 In Vitro

Abstract

Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis.

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

“…In line with our findings, a recent report demonstrated the activity of amantadine against SARS-CoV-2 in VeroE6 cells with EC50 of 83–119 µM [ 32 ]. Our study adds novel knowledge to the field by also investigating rimantadine and memantine, both showing potency superior to amantadine.…”

A Drug Repurposing Approach for Antimalarials Interfering with SARS-CoV-2 Spike Protein Receptor Binding Domain (RBD) and Human Angiotensin-Converting Enzyme 2 (ACE2)

“…The activities of the compounds showing the highest affinity for the RBD were investigated using an ELISA-based test involving immobilized ACE2-His-tag protein on nickel-coated microplates [51][52][53]. This experiment enables the study of the effect of a ligand on the assembly generated by the interaction of RBD with ACE2.…”

SARS-CoV-2 envelope-protein corruption of homeostatic signaling mechanisms in mammalian cells

“…While all studies agree on an overall cation selectivity of the channel, there is no consensus on its preference for K + over Na + [21] and whether it is at all permeable to Ca 2+ [17, 21]. In some of these studies it was reported that E-protein-mediated channel fluctuations were inhibited by the antiviral channel blocker amantadine or hexamethylene-amiloride (HMA), and the presence of these compounds also resulted in an attenuation of virus replication in vivo [11,19, 22, 23]. Because of the heterogeneity in the functional data, it is currently difficult to interpret these pharmacological results in the context of a defined channel activity of the E-protein.…”