A new paradigm for drug discovery in the treatment of complex diseases: drug discovery and optimization

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 24, 2025

Abstract In the past, drug research and development has predominantly followed a "single target, single disease" model. However, clinical data show that single-target drugs are difficult to interfere with complete disease network, prone develop resistance low safety in use. The proposal of multi-target therapy (also known as "cocktail therapy") provides new approach for discovery, which can affect reduce adverse reactions by regulating multiple targets. Natural products an important source innovative development, more than half approved small molecule related natural products. there many challenges process products, such active screening, target identification preclinical dosage optimization. Therefore, how good from always been challenge. This article summarizes applications shortcomings technologies product bioactivity clarify mode action (direct/indirect target), dose Moreover, response faced trend interdisciplinary multi-technology integration, strategy "active substances — optimization" is proposed solve key dimensions levels.

Language: Английский

Integration of metabolomics and chemometrics with in-silico and in-vitro approaches to unravel SARS-Cov-2 inhibitors from South African plants

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0320415 - e0320415

Published: March 26, 2025

Coronavirus disease (COVID-19) is still a severe concern, especially in Africa with suboptimal intention rates of vaccination. This flagged the requirement plant-based remedies as an alternative treatment. In this study we integrated metabolomics and chemometrics approaches silico vitro to accelerate unravel compounds from commonly used South African plants that may inhibit SARS-CoV-2 main protease. The selected plants, Artemisia afra annua , were found be non-toxic against Vero cells, determined by resazurin cell viability assay. Metabolites profiling revealed eighty-one top three hit compounds, quercetin 3-O-(6“-acetyl-glucoside), 2”-O-acetylrutin, 3-(6”-malonyl-glucoside), had binding affinities -9.3 kcal/mol, -9.5 respectively. 2”-O-acetyl group rutin moiety produces hydrogen bond amide nitrogen His41 side chain carboxylate Cys145, Molecular dynamics simulations stable docked complexes. observations validated bioassay, which ability these 3CLpro. collected analysed data does not only draw special attention surfaced 2”-O-acetylrutin best suitable inhibitor 3CLpro, but also indirectly reveals importance integrating plants.

Language: Английский

High-Throughput Molecular Modeling and Evaluation of the Anti-Inflammatory Potential of Açaí Constituents against NLRP3 Inflammasome

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8112 - 8112

Published: July 25, 2024

The search for bioactive compounds in natural products holds promise discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (

Language: Английский