Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.04.237255v1?rss=1 Authors: Kitagawa, T., Mastumoto, A., Terashima, I., Uesono, Y. Abstract: Antimalarial drugs have antimicrobial, antiviral, antimalarial and immunosuppressive activities, although the mechanisms remain unknown. Quinacrine (QC) increases the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localizes in membranes and induces glucose starvation by noncompetitively inhibiting glucose uptake. A logarithmic increase in antimicrobial activity with pH-dependent CAD formation was also observed for chloroquine, indicating that the CAD structure is crucial for its pharmacological activity. A decrease in CAD structure with a slight decrease in pH from 7.4 greatly reduced their effects; namely, these drugs would inefficiently act on falciparum malaria and COVID-19 pneumonia patients with acidosis, resulting in resistance. Recovering normal blood pH or using pH-insensitive quinoline drugs might be effective. Copy rights belong to original authors. Visit the link for more info