Multiscale Process Modelling in Translational Systems Biology of Leishmania major: A Holistic view.

ABSTRACT: Present work aims to utilize systems biology and molecular modelling approach to understand the inhibition kinetics of Leishmania major GLO I and identifying potential hit followed by their validation through in vitro and animal studies. Simulation of GLO I inhibition has shown to affect reaction fluxes of almost all reactions in the model that led to increased production of various AGEs and free radicals. Further, in vitro testing of C1 and C2, selected through molecular modelling revealed remarkable morphological alterations like size reduction, membrane blebbing and loss in motility of the parasite, however, only C1 showed better antileishmanial activity. Additionally, C1 showed apoptosis mediated leishmanicidal activity (apoptosis-like cell death) along with cell-cycle arrest at sub-G0

SUBMITTER: Chauhan N 

PROVIDER: S-EPMC6972910 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature