[Anti-inflammatory effects of amantadine and memantine in SARS-CoV-2 infection]

Amantadine and memantine, apart from their action on cholinergic receptors and dopamine secretion, have a significant influence on the inflammatory process, including the so-called "cytokine storm" and reduction of apoptosis and oxidative stress. Amantadine also inhibits the induction of inflammatory factors such as RANTES, activates kinase p38 of mitogen-activated protein (MAP) and c-Jun-NH2-terminal kinases (JNK), which inhibit viral replication. It also significantly inhibits the entry of SARS-CoV-2 into the bronchial epithelial cell and blocks the viroporin proton channel of the virus. In addition, it has the ability to pass through the membrane of lysosomes into their interior and act as an alkalizing agent, which prevents the release of viral RNA into the cell, which may be a key element in therapeutic management. Memantine also reduces inflammation, mainly in the nervous system, but also acts as a lysosomotropic factor, inhibiting viral replication. However, it is important to bear in mind when undertaking amantadine or memantine therapy with side effects that may overlap with COVID- 19 symptoms, worsening the condition of patients. Currently, the effectiveness of amantadine and memantine in the treatment of patients with COVID-19 symptoms has been demonstrated in a few clinical trials, mainly in patients treated for neurodegenerative diseases. The obtained results are of considerable value, but require confirmation in further studies.