relacatib (GSK-462795) / GSK - LARVOL DELTA

Repurposing Clinical Candidates for Nipah and Hendra Viruses. (PubMed, ACS Infect Dis) - "The clinical-stage cathepsin L inhibitor relacatib exhibited sub-micromolar to nanomolar inhibition of NiV and HeV and was substantially more potent than the nucleoside analogue control favipiravir in vitro. Despite favorable in vitro potency, neither relacatib nor pyronaridine conferred protection in vivo under the tested dosing regimens, a result in part attributable to limited unbound systemic exposure and rapid clearance rather than definitive biological inefficacy. Taken together, this study provides a clinically relevant assessment of host-directed entry inhibition for virulent henipaviruses, highlights key pharmacological barriers to in vivo translation, and offers empirical guidance for prioritizing future antiviral development efforts against NiV and HeV."

Journal • CNS Disorders • Infectious Disease

Unravelling the Relacatib activity against the CTSK proteins causing pycnodysostosis: a molecular docking and dynamics approach. (PubMed, J Biomol Struct Dyn) - "Finally, Molecular dynamics simulations were done in duplicates to recognize the variant (Y283C) activity of the protein structure against Relacatib for 100 ns. This study assists in comprehending the most pathogenic amino-acid variant, the ligand interaction with the protein structure, and paves the way for understanding the steadiness of the ligand with the native and selected significant amino-acid variant.Communicated by Ramaswamy H. Sarma."

Journal • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Osteoarthritis • Osteoporosis • Pain • Rare Diseases • Rheumatology • CTSK