PLoS pathway: proteasome inhibitors are expected to treat drug-resistant malaria

June 12, 2019 / Biovalley / a recent study published in PLoS patterns shows that proteasome inhibitors, in combination with other drugs, have potential in the treatment of multidrug-resistant malaria The study was conducted by David fidock, Caroline ng, Barbara stokes of Irvine Medical Center, Columbia University and Matthew bogyo of Stanford University Medical School Work together with their colleagues Photo source: the drug-resistant malaria caused by Plasmodium protozoa is spreading throughout Southeast Asia Therefore, it is urgent to develop new treatment programs and use compounds that are not affected by the existing anti malarial drug resistance mechanism Recent studies have identified Plasmodium falciparum proteasome as a promising drug target In this new study, the researchers described the antimalarial activities of two selective proteasome inhibitors of Plasmodium falciparum, covalent peptide vinyl sulfone wll vs (WLL) and WLW vs (WLW) These inhibitors showed strong antimalarial activity against drug-resistant Plasmodium falciparum, which is traditionally difficult to treat In addition, unlike many advanced antimalarial candidates, parasites are not easy to gain resistance to these proteasome inhibitors No cross resistance to the two compounds has been found; in fact, partial resistance to one compound often leads to an allergy to the other These data can be explained by the activity analysis of proteasome complexes and the molecular model of proteasome interaction with these inhibitors The results also revealed the synergistic effect between these proteasome inhibitors and a variety of chemically different antimalarial drugs The authors suggest that these results highlight the potential of targeting Plasmodium proteasome with small molecular inhibitors as a means of combating multidrug-resistant malaria Reference: Da Fonseca PCA, et al (2019) valuable plasma false selective protection investors exhibit a low dependency for generating resistance in vitro and synergize with multiple essential agents PLoS pathog 15 (6): e1007722 Doi.org/10.1371/journal.ppat.1007722