The Binding of Brazilin from C. sappan to the Full-Length SARS-CoV-2 Spike Proteins

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4100 - 4100

Published: April 25, 2025

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global issue since 2019. prominent characteristic SARS-CoV-2 is the presence spike (S) protein protruding from virus particle envelope. S major drug and vaccine target because it initiates key step in infection. Medicinal herbs are potential treatment option to enhance immunity fight viral infections. Caesalpinia sappan L. been reported display promising anti-viral activities. Specifically, brazilin (BRA), bioactive compound C. sappan, was play role inhibiting Thus, ability BRA as COVID-19 tested. used this work. Understanding binding mechanism crucial for future utilisation or other coronavirus-caused pandemics. Here, we performed molecular docking onto receptor domain (RBD) multimerisation (MM) pockets. Molecular dynamics (MD) simulations were conducted study stability glycosylated non-glycosylated constructs. can bind Receptor-binding motif (RBM) on an RBD surface stably; however, too large fit into MM pocket, resulting dissociation. Nonetheless, bound residues near S1/S2 interface. We found that glycosylation no effect binding, proposed site far any glycans. Our results thus indicate may act preventive therapeutic alternative treatment.

Language: Английский

Structure-Based Drug Discovery

Advances in medical technologies and clinical practice book series, Journal Year: 2024, Volume and Issue: unknown, P. 435 - 472

Published: Oct. 25, 2024

Structure-Based Drug Discovery (SBDD) leverages the 3D structures of biological targets to design and optimize drug candidates. This chapter reviews SBDD's core principles, historical milestones, modern enhancements. Techniques like X-ray crystallography NMR spectroscopy provide atomic-level insights into drug-target interactions. Computational tools, such as molecular docking virtual screening, improve efficiency safety in discovery. The integration AI cryo-electron microscopy has accelerated progress. Emphasizing physical organic chemistry, SBDD enhances personalized medicine by creating tailored treatments based on genetic profiles.

Language: Английский

Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 1065 - 1065

Published: Dec. 19, 2024

The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing neurotransmitter acetylcholine (ACh). inhibition AChE has emerged as promising therapeutic approach for management neurological disorders such Lewy body dementia and Alzheimer’s disease. potential various compounds inhibitors was investigated. In this study, we evaluated impact natural interest on intrinsic deformability human using computational biophysical analysis. Our incorporates classical dynamics, elastic networks (ENM NMA), statistical potentials (CUPSAT SWOTein), energy frustration (Frustratometer), volumetric cavity analyses (MOLE PockDrug). results revealed that cyanidin induced significant changes flexibility rigidity AChE, especially distribution volume internal cavities, compared to model TZ2PA6, through distinct biophysical-molecular mechanism from other considered. These findings suggest could offer mechanistic pathways future research applications development new treatments neurodegenerative diseases.

Language: Английский