Improving Drug Sensitivity of HIV-1 Protease Inhibitors by Restriction of Cellular Efflux System in a Fission Yeast Model.

ABSTRACT: Fission yeast can be used as a cell-based system for high-throughput drug screening. However, higher drug concentrations are often needed to achieve the same effect as in mammalian cells. Our goal here was to improve drug sensitivity so reduced drugs could be used. Three different methods affecting drug uptakes were tested using an FDA-approved HIV-1 protease inhibitor (PI) drug Darunavir (DRV). First, we tested whether spheroplasts without cell walls increase the drug sensitivity. Second, we examined whether electroporation could be used. Although small improvements were observed, neither of these two methods showed significant increase in the EC₅₀ values of DRV compared with the traditional method. In contrast, when DRV was tested in a mutant strain PR836 that lacks key protei

SUBMITTER: Zhang J 

PROVIDER: S-EPMC9318301 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature