SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease
Zika virus (ZIKV) is a member of the Flaviviridae family that can cause neurological disorders and congenital malformations.
IRBM, working with the University of Rome’s Department of Biology, examined signaling pathways involved with the regulation of Fibro/Adipogenic Progenitors (FAPs). FAPs are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, FAP adipogenesis goes awry, causing fat infiltrates and muscle degeneration. By combining pharmacological screening, high-dimensional mass cytometry and in silico network modelling with the integration of single-cell/bulk RNA sequencing data, the canonical WNT/GSK/β-catenin signaling was highlighted as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. This suggests FAPs have potential in mediating autocrine/paracrine responses in the muscle niche.