Identification of novel bioinspired synthetic mosquito repellents by combined ligand-based screening and OBP-structure-based molecular docking

Thireou, Trias; Kythreoti, Georgia; Tsitsanou, Katerina E.; Koussis, Konstantinos; Drakou, C.E.; Kinnersley, Julie; Kröber, Thomas; Guérin, Patrick M.; Zhou, Jing‐Jiang; Iatrou, Kostas; Eliopoulos, Elias; Zographos, S.E.

doi:10.1016/j.ibmb.2018.05.001

Cited by 37 publications

(31 citation statements)

References 66 publications

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“…15,16 Its action against OBPs has been extensively investigated as an attractive approach to developing novel bio-inspired repellent compounds by combining ligand- and structure-based approaches. 17,18 However, different studies have reported behavioral insensitivity of different insect species to DEET, which could implicate some inefficiency in its repellency activity. 19−21…”

Section: Introductionmentioning

confidence: 99%

Exploring the Potentiality of Natural Products from Essential Oils as Inhibitors of Odorant-Binding Proteins: A Structure- and Ligand-Based Virtual Screening Approach To Find Novel Mosquito Repellents

et al. 2019

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Odorant-binding proteins (OBPs) are the main olfactory proteins of mosquitoes, and their structures have been widely explored to develop new repellents. In the present study, we combined ligand- and structure-based virtual screening approaches using as a starting point 1633 compounds from 71 botanical families obtained from the Essential Oil Database (EssOilDB). Using as reference the crystallographic structure of N,N-diethyl-meta-toluamide interacting with the OBP1 homodimer of Anopheles gambiae (AgamOBP1), we performed a structural and pharmacophoric similarity search to select potential natural products from the library. Thymol acetate, 4-(4-methyl phenyl)-pentanal, thymyl isovalerate, and p-cymen-8-yl demonstrated a favorable chemical correlation with DEET and also had high-affinity interactions with the OBP binding pocket that molecular dynamics simulations showed to be stable. To the best of our knowledge, this is the first study to evaluate on a large scale the potentiality of NPs from essential oils as inhibitors of the mosquito OBP1 using in silico approaches. Our results could facilitate the design of novel repellents with improved selectivity and affinity to the protein binding pocket and can shed light on the mechanism of action of these compounds against insect olfactory recognition.

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Section: Introductionmentioning

confidence: 99%

Exploring the Potentiality of Natural Products from Essential Oils as Inhibitors of Odorant-Binding Proteins: A Structure- and Ligand-Based Virtual Screening Approach To Find Novel Mosquito Repellents

et al. 2019

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“…Despite these molecular filters having been widely applied in virtual screening approaches to select natural products from large chemo-structural libraries (Thireou et al, 2018 ; Da Costa et al, 2019 ; Galúcio et al, 2019 ), caution must be taken to avoid remotion of the chemo-structures with appropriate bioavailability (Shultz, 2019 ). Most natural products break some chemical rules applied in molecular filtering; furthermore, some chemical classes of compounds, such as peptides and polyketides (e.g., macrolides), are located beyond the chemical limits determined by the rule of five (beyond the rule of five, bRO5) (Doak et al, 2014 ; Naylor et al, 2017 ; Rossi Sebastiano et al, 2018 ).…”

Section: Computational Methods Applied In Virtual Screening Approachesmentioning

confidence: 99%

“…Pharmacophoric screening has been applied to screen compounds with cosmetic purposes using essential oils (Santana et al, 2018 ; Da Costa et al, 2019 ). Essential oils contain diverse classes of volatile and low-molecular-weight compounds with a broad spectrum of biological activities (Do Nascimento et al, 2020 ), and due to their reported repellent activities against mosquitos, these compounds have been investigated in virtual screening strategies (Santana et al, 2018 ; Thireou et al, 2018 ). Recently, a study performed an in silico analysis of 1,633 compounds from the essential oils of 71 botanical families by combining a structural similarity-based search method (ligand-based virtual screening) with a pharmacophore-based virtual screening (structure-based strategy).…”

Section: Computational Methods Applied In Virtual Screening Approachesmentioning

confidence: 99%

“…Shape-based similarity methods have been used in virtual screening workflows alone or combined with different computational techniques (Pavadai et al, 2017 ; Thireou et al, 2018 ). Pavadai et al applied shape-based and fingerprint-based similarity search against natural product libraries to find new steroid-like natural products as antiplasmodial agents using, as a search key, fusidic acid.…”

Section: Computational Methods Applied In Virtual Screening Approachesmentioning

confidence: 99%

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Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

et al. 2021

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Natural products are continually explored in the development of new bioactive compounds with industrial applications, attracting the attention of scientific research efforts due to their pharmacophore-like structures, pharmacokinetic properties, and unique chemical space. The systematic search for natural sources to obtain valuable molecules to develop products with commercial value and industrial purposes remains the most challenging task in bioprospecting. Virtual screening strategies have innovated the discovery of novel bioactive molecules assessing in silico large compound libraries, favoring the analysis of their chemical space, pharmacodynamics, and their pharmacokinetic properties, thus leading to the reduction of financial efforts, infrastructure, and time involved in the process of discovering new chemical entities. Herein, we discuss the computational approaches and methods developed to explore the chemo-structural diversity of natural products, focusing on the main paradigms involved in the discovery and screening of bioactive compounds from natural sources, placing particular emphasis on artificial intelligence, cheminformatics methods, and big data analyses.

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“…Further present findings agree with those earlier studies ofCarey et al (2010) reported that the some plant-derived repellents have been found to target multiple odorant receptors. Expected to be less susceptible to resistance than compounds acting on a single receptor (Norris and Coats 2017) Thireou et al (2018). studied a fast and efficient virtual screening protocol for discovery of novel bioinspired synthetic mosquito repellents with lower volatility and, in all likelihood, increased protection time as compared with their plant-derived parental compounds.Adultcidal activityAdulticidal activity of p.ether, acetone and ethanol leaf extract of S. zeylanica against adult of An.…”

mentioning

confidence: 99%

Molecular Interaction of Novel Phytocompounds From Smilax Zeylanica (L) Against the Targeted Protein of Mosquito Vectors and Their Potential Activity

Chandramohan

Murugan

Madhiyazhagan

et al. 2022

Preprint

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Malaria, dengue fever, filariasis, and viral encephalitis are all mosquito-borne illnesses that cause a great number of health issues across the world. Mosquitoes inject saliva into their hosts' skin to make obtaining a blood meal simpler by inhibiting hemostasis. D7 proteins are abundant in mosquito saliva and act as biogenic amine and eicosanoids scavengers. The chemical interactions of possible Smilax zeylanica compounds with mosquito-targeted D7 salivary protein and odorant binding protein were investigated. From petroleum ether, acetone, and ethanolic solvents, a total of 28 chemical components were discovered in the GC-MS study of S . zeylanica . Different solvents were also tested for their adulticidal and repellent properties against Anopheles stephensi, Aedes aegypti , and Culex quinquefasciatus . Among the three solvents, the ethanolic extract exhibited the highest toxic level against the three mosquito species. LC 50 of P. ether 284.92ppm, 311.97ppm and 332.76ppm; LC 50 of acetone 241.97ppm, 271.61ppm and 304.99ppm; and LC 50 of ethanol 217.12ppm, 241.89ppm and 266.90ppm, against the three mosquito species, respectively. In repellent activity from all the solvents, complete protection was observed for up to 150 minutes against the three mosquito species. A total of 22 compounds were taken for docking studies. The compounds were subjected to docking against the three mosquitoes' D7protein. Overall, this study highlights the importance of a computational approach based on control of mosquito vectors and potential activity of biopesticides.

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Identification of novel bioinspired synthetic mosquito repellents by combined ligand-based screening and OBP-structure-based molecular docking

Cited by 37 publications

References 66 publications

Exploring the Potentiality of Natural Products from Essential Oils as Inhibitors of Odorant-Binding Proteins: A Structure- and Ligand-Based Virtual Screening Approach To Find Novel Mosquito Repellents

Exploring the Potentiality of Natural Products from Essential Oils as Inhibitors of Odorant-Binding Proteins: A Structure- and Ligand-Based Virtual Screening Approach To Find Novel Mosquito Repellents

Applications of Virtual Screening in Bioprospecting: Facts, Shifts, and Perspectives to Explore the Chemo-Structural Diversity of Natural Products

Molecular Interaction of Novel Phytocompounds From Smilax Zeylanica (L) Against the Targeted Protein of Mosquito Vectors and Their Potential Activity

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