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Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance. In vitro studies performed on cellular models of multiple myeloma (MM) strengthened our hypothesis by highlighting that the antiproliferative and apoptotic effect induced by the treatment with RSV is associated with an increase of TERRA transcript and with upregulation of telomeric heterochromatin markers, such as H3K27Me3 and H4K20Me3, and of the hallmark of apoptosis, cleaved-poly(ADP-ribose) polymerase-1. Our results propose innovative insights underlying the multifaceted role of RSV in MM, by pointing out the role of this natural compound in an lncRNA-mediated regulation to counteract cellular immortality., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

The growing information currently available on the central role of non-coding RNAs (ncRNAs) including microRNAs (miRNAS) and long non-coding RNAs (lncRNAs) for chronic and degenerative human diseases makes them attractive therapeutic targets. RNAs carry out different functional roles in human biology and are deeply deregulated in several diseases. So far, different attempts to therapeutically target the 3D RNA structures with small molecules have been reported. In this scenario, the development of computational tools suitable for describing RNA structures and their potential interactions with small molecules is gaining more and more interest. Here, we describe the most suitable strategies to study ncRNAs through computational tools. We focus on methods capable of predicting 2D and 3D ncRNA structures. Furthermore, we describe computational tools to identify, design and optimize small molecule ncRNA binders. This review aims to outline the state of the art and perspectives of computational methods for ncRNAs over the past decade., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roberta Rocca reports financial support was provided by Italian Association for Cancer Research. Stefano Alcaro reports financial support was provided by PRIN., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)