Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators

Abstract

Abstract:This review aims to summarize the latest efforts performed in the search for novel chemical entities such as Toll-like receptor (TLR) modulators by means of virtual screening techniques. This is an emergent research field with only very recent (and successful) contributions. Identification of drug-like molecules with potential therapeutic applications for the treatment of a variety of TLR-regulated diseases has attracted considerable interest due to the clinical potential. Additionally, the virtual screening databases and computational tools employed have been overviewed in a descriptive way, widening the scope for researchers interested in the field.

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…In this regard, Mancek-Keber and Jerala [148] have proposed three postulates to distinguish direct agonists from indirect activators: (1) the agonist requires the TLR-4/MD-2 receptor complex; (2) either synthetically or in situ, they must activate the receptor complex in order to eliminate artefacts from other agonists; and (3) a specific molecular interaction between the agonist and TLR-4/MD-2 must be identified. Furthermore, in 2016 the group of Martin-Santamaria [149,150] proposed to use computational approaches [149] and big databases [150] for the identification of all atomic details in the TLR-4 receptor structure itself and the ligand-receptor interactions of different modulators to develop novel agonists and antagonists with promising biomedical applications, to reduce toxic effects, and improve drug-like properties, fine-tuning of relative potency of agonists and antagonists, binding capacity and specificity.…”

“…Similar considerations may also be valid for small natural molecules, such as curcumin, cinnamaldehyde and sulforaphane, which have been reported to mediate the anti-TLR4 dimerization effects, as well as for resveratrol and some flavonoids (such as EGCG, lutelolin, quercetin, chrysin, and eriodictyol), that have been reported to inhibit TBK1 kinase activity (a downstream TLR4 signaling kinase), resulting in a decreased IRF3 activation, a TLR4 signaling adaptator, and target gene expression [101][102][103][104]150] (see Table 5). …”

Inhibition of polyamine biosynthesis for toxicity control in Serratia marcescens strain WW4 by targeting ornithine decarboxylase: a structure-based virtual screening study

“…Structure-based virtual screening (SBVS) (Huang et al, 2015;Zhang et al, 2012) was used to exploit the molecular recognition between the ligands and ODC to select chemical entities that bind strongly to the active sites (Daidone et al, 2012;Pérez-Regidor et al, 2016). This approach used docking and scoring to sort the candidates in a virtual library.…”

Data Analysis in Chemistry and Bio-Medical Sciences

“…The issue focuses on the development and application of different theoretical algorithms combining chemoinformatics, computational chemistry, bioinformatics, and data analysis methods. In the issue, we present a total of 18 papers with full versions of the communications presented at the conference as well as papers of other authors worldwide (direct submissions) [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. …”

“…A team lead by Martín-Santamaría [17], from Centro de Investigaciones Biológicas, CIB-CSIC, Spain (*), reviewed the virtual screening methods for the discovery of toll-like receptor modulators. This review focused on the search for novel chemical entities such as modulators of Toll-like receptor (TLR) by means of virtual screening techniques.…”