Multivariate chemogenomic screening prioritizes new macrofilaricidal leads.

ABSTRACT: Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential. We developed a multivariate screen that identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of >50% by leveraging abundantly accessible microfilariae. Adult assays were multiplexed to thoroughly characterize compound activity across relevant parasite fitness traits, including neuromuscular control, fecundity, metabolism, and viability. Seventeen compounds from a diverse chemogenomic library elicited strong effects on at least one adult trait, with diffe

SUBMITTER: Wheeler NJ 

PROVIDER: S-EPMC9839782 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature