Repurposing Amantadine and Memantine for COVID-19: Guanylate Kinases Might Pave the Road towards Novel SARS CoV-2 and Anti Neoplastic Therapeutics.

New abstract: Severe and critical COVID-19 represents a medical challenge that is often lost due to the lack of efficient pharmacotherapy. Amantadine and memantine are suggested to administered first in clinical trials for selected severe and critical COVID-19 patients and a novel hypothesis that might explain their potential benefits is provided together with the other suggested mechanisms. Old abstract: Guanylate kinase 1 (GK) was suggested to play a crucial role in SARS CoV-2 replication and previous studies have suggested a role in the pathogenesis of some neoplasms. We are providing a concise strengths, weaknesses, opportunities, and threats (SWOT) analysis of this hypothesis while discussing guanylate kinase physiological function, pharmacological importance. Importantly, though GK1 role in SARS CoV-2 replication might prove valid, the available experimental inhibitors of GK 1 might not, at least for the short term, be safely used to manage COVID-19. However, we suggest assessing another potential interaction between SARS CoV-2 and the non-authentic membrane-associated guanylate kinases as we suggest this might add to consider the potential role of the NMDA antagonists amantadine and memantine in COVID-19 management for and we have recommended clinical trials for selected described COVID-19 patients. Finally, we also recommend conducting genetic, physiological, and immunological studies to explore the long-term potentials of novel GK-1 inhibitors suggesting they might eventually lead to a novel COVID-19 and cancer pharmacotherapeutics.