key: cord-1000668-niarg67j
authors: Hasanagic, Senad; Serdarevic, Fadila
title: Potential role of memantine in the prevention and treatment of COVID-19: its antagonism of nicotinic acetylcholine receptors (nAChR) and beyond
date: 2020-06-18
journal: Eur Respir J
DOI: 10.1183/13993003.01610-2020
sha: 5abbc3e993568bae97b0b777f115d0ac03e63fae
doc_id: 1000668
cord_uid: niarg67j

Memantine, as an antagonist of α7-nAChR and NMDA receptors may decrease ACE2 receptors expression and reduce oxidative stress and inflammation. Hence, memantine may potentially reduce SARS-CoV-2 virulence.

Memantine, in addition to its noncompetitive NMDA receptors antagonism, is very potent α7-nAChR antagonist (5) . By its α7-nAChR antagonism it blocks meningitic E. coli K1 bacteria neuroinvasion in mice (5) . Also it may exerts its protective, anti-inflammatory effects by suppression of cytokine expression, as demonstrated in an experimental model of lung injury (6) . As an adamantine derivate, in cell cultures memantine inhibits Human coronaviruse strain OC43 (HCoV-OC43) replication after virus attachment to the cell receptor, acting as an antiviral drug (7) . Infection with HCoV-OC43, in particular mutated surface protein S, increases level of inflammation by release of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1, interleukin 6 and by inducing microphage/microglial hyper-activation in central nervous system (7, 8) . Memantine may counteract these deleterious effects by inhibiting activity of microglia (8, 9) Moreover neuroinvasion with mutated surface protein S variants of HCoV-OC43 resulted in paralysis of experimental animals due to glutamate excitotoxicity. Memantine ameliorated these motor disturbances, reduced mortality rates and inhibited corona virus replication rate in the central nervous system, dose-dependently (7, 9) . Also memantine might exert anti-inflammatory effects by reducing angiogenesis and brain lymphocyte infiltration, as shown in mice infected with Japanese encephalitis virus (JEV) (10) . In conclusion, we might hypothesize that memantine may reduce virulence and pathogenicity of SARS-Cov-2 and potentially exert its effects both in lungs and brain, however such claims require further thorough experimental, epidemiological and clinical confirmations.

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This study is not financially supported.