Novel small molecule agonists of an<i>Aedes aegypti</i>neuropeptide Y receptor block mosquito biting behavior

Duvall, Laura B.; Ramos‐Espiritu, Lavoisier; Barsoum, Kyrollos E.; Glickman, J. Fraser; Vosshall, Leslie B.

doi:10.1101/393793

Cited by 4 publications

(3 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ligands L46, L66 and L68 (see Figure 9) were tested via a high-throughput screening (HTS) assay based on primary cells, for identification of small molecule agonists of Aedes aegypti NPYLR7 [Small Molecule Inhibitors of Behavior of Mosquito Bites], a mouse cGAS RapidFire screen, human cGAS chemiluminescence screen, and the molecules were considered inactive in these analyzes [62,63,64,65].…”

Section: Resultsmentioning

confidence: 99%

Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos

et al. 2019

View full text Add to dashboard Cite

Aedes aegypti (Linnaeus, 1762; Diptera: Culicidae) is the main vector transmitting viral diseases such as dengue fever, dengue haemorrhagic fever, urban yellow fever, zika and chikungunya. Worldwide, especially in the Americas and Brazil, many cases of dengue have been reported in recent years, which have shown significant growth. The main control strategy is the elimination of the vector, carried out through various education programs, to change human habits, but the most usual is biological control, together with environmental management and chemical control. The most commonly insecticide used is temephos (an organophosphorus compound), but Aedes aegypti populations have shown resistance and the product is highly toxic, so we chose it as a template molecule to perform a ligand-based virtual screening in the ChemBrigde (DIVERSet-CL subcollection) database, searching for derivatives with similarity in shape (ROCS) and electrostatic potential (EON). Thus, fourty-five molecules were filtered based on their pharmacokinetic and toxicological properties and 11 molecules were selected by a molecular docking study, including binding affinity and mode of interaction. The L46, L66 and L68 molecules show potential inhibitory activity for both the insect (−9.28, −10.08 and −6.78 Kcal/mol, respectively) and human (−6.05, 6.25 and 7.2 Kcal/mol respectively) enzymes, as well as the juvenile hormone protein (−9.2; −10.96 and −8.16 kcal/mol, respectively), showing a significant difference in comparison to the template molecule temephos. Molecules L46, L66 and L68 interacted with important amino acids at each catalytic site of the enzyme reported in the literature. Thus, the molecules here investigated are potential inhibitors for both the acetylcholinesterase enzymes and juvenile hormone protein–from insect and humans, characterizing them as a potential insecticide against the Aedes aegypti mosquito.

show abstract

Section: Resultsmentioning

confidence: 99%

Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The titer of A. aegypti NPF in the haemolymph is influenced by feeding and decreases drastically after a blood meal (60). Recent studies indicate that genetic and pharmacological disruption of the mosquito NPF pathway results in abnormal host-seeking behavior and blood-feeding (61).…”

Section: The (Long) Npf Signaling System and Its Role In Feeding And mentioning

confidence: 99%

Regulation of Feeding and Metabolism by Neuropeptide F and Short Neuropeptide F in Invertebrates

et al. 2019

View full text Add to dashboard Cite

Numerous neuropeptide systems have been implicated to coordinately control energy homeostasis, both centrally and peripherally. However, the vertebrate neuropeptide Y (NPY) system has emerged as the best described one regarding this biological process. The protostomian ortholog of NPY is neuropeptide F, characterized by an RXRF(Y)amide carboxyterminal motif. A second neuropeptide system is short NPF, characterized by an M/T/L/FRF(W)amide carboxyterminal motif. Although both short and long NPF neuropeptide systems display carboxyterminal sequence similarities, they are evolutionary distant and likely already arose as separate signaling systems in the common ancestor of deuterostomes and protostomes, indicating the functional importance of both. Both NPF and short-NPF systems seem to have roles in the coordination of feeding across bilaterian species, but during chordate evolution, the short NPF system appears to have been lost or evolved into the prolactin releasing peptide signaling system, which regulates feeding and has been suggested to be orthologous to sNPF. Here we review the roles of both NPF and sNPF systems in the regulation of feeding and metabolism in invertebrates.

show abstract

“…Indeed, both laboratory and field observations showed that, given the opportunity, mated females accept a second blood meal while the first blood meal is still being digested and females feed every 2.5 days on average 10,12,23 . This is in contrast with other hematophagous insects, such as mosquitoes, where female host-seeking and feeding are suppressed for several days after a blood meal, until she completes laying a batch of eggs 17,24 .…”

Section: Discussionmentioning

confidence: 88%

Mating and starvation modulate feeding and host-seeking responses in female bed bugs,Cimex lectularius

Saveer

DeVries

Santangelo

et al. 2020

Preprint

View full text Add to dashboard Cite

Adaptive insect behavior is subject to modulation by internal physiological states and external social contexts to enhance reproductive fitness and survival. The common bed bug, Cimex lectularius is an obligate hematophagous ectoparasite that requires host blood for growth, development, and reproduction. We investigated how mating, starvation and social factors such as harassment by males affect host-seeking, blood feeding, oviposition, and survival of female bed bugs. The percentage of females that fed and the amount of blood they ingested were greater in mated females (90 to 100%) than in unmated females (48 to 60%). Mating state also modulated the females orientation towards human skin odor in an olfactometer; more mated (69%) than unmated (23%) females responded to human odors. The response rate of unmated females (60%) to human odor increased with longer starvation period, while the opposite pattern was observed in mated females (20%). Although fecundity after a single blood meal was unaffected by long or short residence with males, females subjected to frequent copulations had lower survivorship and lifespan than females subjected to males for only 24 h. Taken together, these results indicate that behaviors are adaptively expressed based on the internal physiological state to maximize survival and reproductive fitness.

show abstract

Novel small molecule agonists of anAedes aegyptineuropeptide Y receptor block mosquito biting behavior

Cited by 4 publications

References 67 publications

Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos

Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos

Regulation of Feeding and Metabolism by Neuropeptide F and Short Neuropeptide F in Invertebrates

Mating and starvation modulate feeding and host-seeking responses in female bed bugs,Cimex lectularius

Contact Info

Product

Resources

About