Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	2D finger-printing and molecular docking studies identified potent mosquito repellents targeting odorant binding protein 1
Δημιουργός/Συγγραφέας:	Liggri, Panagiota G V Pérez-Garrido, Alfonso Tsitsanou, Katerina E Dileep, Kalarickal V Michaelakis, Antonios Papachristos, Dimitrios P Pérez-Sánchez, Horacio [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E.
Ημερομηνία:	2023-06
Γλώσσα:	Αγγλικά
ISSN:	09651748
DOI:	10.1016/j.ibmb.2023.103961
Άλλο:	37217081
Περίληψη:	Personal protection measures against the mosquitoes like the use of repellents constitute valuable tools in the effort to prevent the transmission of vector-borne diseases. Therefore, the discovery of novel repellent molecules which will be effective at lower concentrations and provide a longer duration of protection remains an urgent need. Mosquito Odorant-Binding Proteins (OBPs) involved in the initial steps of the olfactory signal transduction cascade have been recognized not only as passive carriers of odors and pheromones but also as the first molecular filter to discriminate semiochemicals, hence serving as molecular targets for the design of novel pest control agents. Among the three-dimensional structures of mosquito OBPs solved in the last decades, the OBP1 complexes with known repellents have been widely used as reference structures in docking analysis and molecular dynamics simulation studies for the structure-based discovery of new molecules with repellent activity. Herein, ten compounds known to be active against mosquitoes and/or displaying a binding affinity for Anopheles gambiae AgamOBP1 were used as queries in an in silico screening of over 96 million chemical samples in order to detect molecules with structural similarity. Further filtering of the acquired hits on the basis of toxicity, vapor pressure, and commercial availability resulted in 120 unique molecules that were subjected to molecular docking studies against OBP1. For seventeen potential OBP1-binders, the free energy of binding (FEB) and mode of interaction with the protein were further estimated by molecular docking simulations leading to the selection of eight molecules exhibiting the highest similarity with their parental compounds and favorable energy values. The in vitro determination of their binding affinity to AgamOBP1 and the evaluation of their repellent activity against female Aedes albopictus mosquitoes revealed that our combined ligand similarity screening and OBP1 structure-based molecular docking successfully detected three molecules with enhanced repellent properties. A novel DEET-like repellent with lower volatility (8.55 × 10-4 mmHg) but a higher binding affinity for OBP1 than DEET (1.35 × 10-3 mmHg). A highly active repellent molecule that is predicted to bind to the secondary Icaridin (sIC)-binding site of OBP1 with higher affinity than to the DEET-site and, therefore, represents a new scaffold to be exploited for the discovery of binders targeting multiple OBP sites. Finally, a third potent repellent exhibiting a high degree of volatility was found to be a strong DEET-site binder of OBP1 that could be used in slow-release formulations.
Τίτλος πηγής δημοσίευσης:	Insect biochemistry and molecular biology
Τόμος/Κεφάλαιο:	157
Θεματική Κατηγορία:	[EL] Δομική Βιολογία[EN] Structural Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Βιοτεχνολογία[EN] Biotechnology
Λέξεις-Κλειδιά:	mosquito repellent Odorant binding proteins (OBPs) virtual screening molecular docking molecular dynamics behavioral bioassay
EU Grant:	QFytoTera Operational Programme Education and Lifelong Learning
EU Grant identifier:	Τ1EDK-00996 MIS5000432
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 Elsevier Ltd. All rights reserved.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1016/j.ibmb.2023.103961
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο