@article {Smieszek2020.04.05.026187, author = {Sandra P. Smieszek and Bart P Przychodzen and Mihael H Polymeropoulos}, title = {{\textquotedblleft}Amantadine disrupts lysosomal gene expression; potential therapy for COVID19{\textquotedblright}}, elocation-id = {2020.04.05.026187}, year = {2020}, doi = {10.1101/2020.04.05.026187}, publisher = {Cold Spring Harbor Laboratory}, abstract = {SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in lysosomes).We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson{\textquoteright}s disease. It is available as a generic drug..Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway, hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.}, URL = {https://www.biorxiv.org/content/early/2020/04/05/2020.04.05.026187.1}, eprint = {https://www.biorxiv.org/content/early/2020/04/05/2020.04.05.026187.1.full.pdf}, journal = {bioRxiv} }