Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases

Abstract

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet’s biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

Meridianins Inhibit GSK3β In Vivo and Improve Behavioral Alterations Induced by Chronic Stress

“…Meridianins have been isolated from different specimens of the tunicate genera Aplidium and Synoicum [ 36 , 37 ]; however, it is still unclear whether tunicates are the true producers of the molecules or whether the associated microbes may play a role in their synthesis and chemical ecology [ 28 , 39 ]. The potential of meridianins as bioactive drugs has been reported previously [ 33 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Recently, we showed that meridianins can act as the ATP-competitive or non-ATP-competitive inhibitors of GSK3β in vitro without altering neuronal survival [ 54 ].…”

Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis

“…The role of CADD in cardiovascular diseases : Cardiovascular diseases (CVD) are considered the first cause of death globally 178 . It is common to have significant coronary heart disease, myocardial ischemia and hypertension, as well as diabetes-related complications 179 .…”

Virtual Insights into Natural Compounds as Potential 5α-Reductase Type II Inhibitors: A Structure-Based Screening and Molecular Dynamics Simulation Study

“…However, despite the advancements made in informatics and computational biology, as well as parallel increases in drug development productivity, drug development has been sluggish due to heavy dependence on synthetic small molecules as a source of innovation. Computer-Aided Drug Design (CADD) has emerged as a highly effective technique for identifying promising lead compounds and advancing prospective pharmaceutical medicines addressing a wide range of disorders [13][14][15]. Currently, a variety of computational techniques are being used to identify interesting lead entities from large compound repositories.…”