A systems perspective on ribavirin-induced hemolytic anemia: From network toxicology to atomic-level simulations
Year: 2025
Type: article
Abstract: The molecular mechanisms underlying ribavirin (RBV)-induced hemolytic anemia remain incompletely understood. Current research predominantly addresses individual targets or pathways, lacking a comprehensive integration of multi-target interaction networks. This study employs a combination of network toxicology (NT), multi-scale molecular dynamics (MD) simulation techniques, and in vitro experiments to conduct an in-depth analysis of the multi-target mechanisms responsible for RBV-induced hemolytic anemia. Methods: A multi-scale biological molecular network model was developed utilizing NT. Multi-scale molecular simulations were employed to integrate calculations across various temporal and spatial scales. This approach was complemented by red blood cell hemolysis assays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative analysis, and circular dichroism (CD) spectroscopy experiments, thereby elucidating the hierarchical patterns of molecular behaviors that contribute to RBV-induced hemolytic anemia across multiple scales.Results: The findings demonstrated that RBV/triphenyl ribavirin (RTP) disrupts the function of the Band 3 protein, inhibits glucose-6-phosphate dehydrogenase (G6PD) activity, induces oxidative stress, and triggers apoptotic pathways, ultimately resulting in the rupture of red blood cells. The integration of multi-scale data corroborated the "drug accumulation-oxidative stress-cell death" three-stage damage model, offering a quantitative characterization framework from atomic to systemic levels for elucidating the toxicity mechanism of nucleoside analogues. This approach advances the application of analytical toxicology in the evaluation of drug safety.
Authors: Xumeng SHI, Shijia LU, Guangman ZHU, Tianjiao CUI, Shunhang WU, Mengdan SANG, Yiran ZHEN, Xue YANG, Huaying DU, Miaoyan Han, Mengjia YAN, Jinle WANG, Yutong ZHANG, Jiying DU
Institutions: Henan Medical University, North Henan Medical University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G2711102961, G3167948149, G7765086557
OpenAlex ID: W4416020354