A Chemosensory GPCR as a Potential Target to Control the Root-Knot Nematode Meloidogyne incognita Parasitism in Plants

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 20; p. 3798
• Main Authors: Bresso, Emmanuel, Fernandez, Diana, Amora, Deisy X, Noel, Philippe, Petitot, Anne-Sophie, de Sa, Maria-Eugênia Lisei, Albuquerque, Erika V S, Danchin, Etienne G J, Maigret, Bernard, Martins, Natália F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.10.2019; MDPI
• Subjects: Animals; Antinematodal Agents - chemistry; Antinematodal Agents - metabolism; Antinematodal Agents - pharmacology; Behavior; Binding sites; Chemical Sciences; Cheminformatics; Chemoreception; G protein-coupled receptors; Genome, Helminth; Helices; Helminth Proteins - antagonists & inhibitors; Helminth Proteins - chemistry; Helminth Proteins - genetics; Homology; homology modelling; Host-Parasite Interactions - genetics; In vivo methods and tests; Life Sciences; meloidogyne incognita; Microbiology and Parasitology; molecular dynamics; Molecular Dynamics Simulation; Nematodes; Neuropeptide Y; Neuropeptides; Parasites; Parasitism; Parasitology; Peptides; Phylogenetics; Phylogeny; Phytopathology and phytopharmacy; Plant Diseases - parasitology; Plant Diseases - prevention & control; Plant Roots - parasitology; Protein Structure, Secondary; Proteins; Quantitative Methods; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - genetics; Simulation; Solanum lycopersicum - parasitology; Tylenchoidea - genetics; Vegetal Biology; virtual screening; homology modelling; Meloidogyne incognita; virtual screening; molecular dynamics
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24203798

Root-knot nematodes (RKN), from the genus, have a worldwide distribution and cause severe economic damage to many life-sustaining crops. Because of their lack of specificity and danger to the environment, most chemical nematicides have been banned from use. Thus, there is a great need for new and safe compounds to control RKN. Such research involves identifying beforehand the nematode proteins essential to the invasion. Since G protein-coupled receptors GPCRs are the target of a large number of drugs, we have focused our research on the identification of putative nematode GPCRs such as those capable of controlling the movement of the parasite towards (or within) its host. A datamining procedure applied to the genome of allowed us to identify a GPCR, belonging to the neuropeptide GPCR family that can serve as a target to carry out a virtual screening campaign. We reconstructed a 3D model of this receptor by homology modeling and validated it through extensive molecular dynamics simulations. This model was used for large scale molecular dockings which produced a filtered limited set of putative antagonists for this GPCR. Preliminary experiments using these selected molecules allowed the identification of an active compound, namely C260-2124, from the ChemDiv provider, which can serve as a starting point for further investigations.