# Virtual Screening and Molecular Dynamics of Cytokine–Drug Complexes for Atherosclerosis Therapy

## TL;DR

This study uses computer simulations to find new drug candidates and nutraceuticals that could target inflammatory proteins involved in atherosclerosis.

## Contribution

The study introduces a computational approach for identifying multitarget cytokine inhibitors and highlights promising nutraceuticals for atherosclerosis therapy.

## Key findings

- Virtual screening identified FDA-approved drugs with potential to inhibit TNF-α, IFN-γ, and IL-1β.
- Molecular dynamics simulations confirmed stable interactions between selected ligands and cytokine targets.
- Nutraceutical fatty acids showed strong binding to key cytokines, suggesting therapeutic potential.

## Abstract

Cardiovascular disease remains the leading global cause of mortality, largely driven by atherosclerosis, a chronic inflammatory condition characterized by lipid accumulation and immune-cell infiltration in arterial walls. Macrophages play a central role by forming foam cells and secreting pro-atherogenic cytokines, such as TNF-α, IFN-γ, and IL-1β, which destabilize atherosclerotic plaques, expanding the lipid core and increasing the risk of thrombosis and ischemia. Despite the significant health burden of subclinical atherosclerosis, few targeted therapies exist. Current treatments, including monoclonal antibodies, are limited by high costs and immunosuppressive side effects, underscoring the urgent need for alternative therapeutic strategies. In this study, we employed in silico drug repositioning to identify multitarget inhibitors against TNF-α, IFN-γ, and IL-1β, leveraging a virtual screening of 2750 FDA-approved drugs followed by molecular dynamics simulations to assess the stability of selected cytokine–ligand complexes. This computational approach provides structural insights into potential inhibitors. Additionally, we highlight nutraceutical options, such as fatty acids (oleic, linoleic and eicosapentaenoic acid), which exhibited strong and stable interactions with key cytokine targets. Our study suggests that these bioactive compounds could serve as effective new therapeutic approaches for atherosclerosis.