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The rapidly increasing amount of publicly available knowledge in biology and chemistry enables scientists to revisit many open problems by the systematic integration and analysis of heterogeneous novel data. The integration of relevant data does not only allow analyses at the network level, but also provides a more global view on drug-target relations. Here we review recent attempts to apply large-scale computational analyses to predict novel interactions of drugs and targets from molecular and cellular features. In this context, we quantify the family-dependent probability of two proteins to bind the same ligand as function of their sequence similarity. We finally discuss how phenotypic data could help to expand our understanding of the complex mechanisms of drug action.

Background Aedes aegypti (L.) is an urban mosquito, vector of several arboviruses that cause severe diseases in hundreds of million people each year. The resistance to synthetic insecticides developed by Ae. aegypti populations worldwide has contributed to failures in vector control campaigns, increasing the impact of arbovirus diseases. In this context, plant-derived essential oils with larvicidal activity could be an attractive alternative for vector control. However, the mode of action and the detoxificant response of mosquitoes to plant derived compounds have not been established, impairing the optimization of their use. Methods and findings Here we compare gene expression in Ae. aegypti larvae after 14 hrs of exposure to Eucalyptus camaldulensis essential oil with a control group exposed to vehicle (acetone) for the same lapse, by using RNA-Seq. We found differentially expressed genes encoding for cuticle proteins, fatty-acid synthesis, membrane transporters and detoxificant related gene families (i.e. heat shock proteins, cytochromes P450, glutathione transferases, UDP-glycosyltransferases and ABC transporters). Finally, our RNA-Seq and molecular docking results provide evidence pointing to a central involvement of chemosensory proteins in the detoxificant response in mosquitoes. Conclusions and significance Our work contributes to the understanding of the physiological response of Ae. aegypti larvae to an intoxication with a natural toxic distilled from Eucalyptus leafs. The results suggest an involvement of most of the gene families associated to detoxification of xenobiotics in insects. Noteworthy, this work provides important information regarding the implication of chemosensory proteins in the detoxification of a natural larvicide. Understanding the mode of detoxification of Eucalyptus distilled compounds could contribute to their implementation as a tool in mosquito control.

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Aedes aegypti (L.) (Diptera: Culicidae) is the key vector of three important arboviral diseases: dengue, yellow fever, and chikungunya. Immature stages of this species inhabit human-made containers placed in residential landscapes. In this study, we evaluated a few compounds in a sensitive behavioral assay with Ae. aegypti larvae. The orientation of larvae to different compounds was surveyed using a performance index (PI). The PI represents the response to each odorant, where a value of +1 is indicative of full attraction and -1 represents complete repulsion. The widely used insect repellent N, N-diethyl-m-toluamide elicited a significantly negative PI, as did acetophenone and indole. A yeast extract, a known food source, elicited a significantly positive PI, as did 2-methylphenol, 1-octen-3-ol, 3-methylphenol, and fish food. On the other hand, no response was observed for the essential oil of Eucalyptus grandis x Eucalyptus camaldulensis at the concentration evaluated. Pretreatment of larvae with N-ethylmaleimide and ablation of the antennae resulted in a suppression of behavioral responses. The overall mobility of ablated larvae was indistinguishable from unablated controls, and absence of any visible locomotor dysfunction was observed. This work is a contribution to the study of the chemical ecology of disease vectors with the aim of developing more efficient tools for surveillance and control.Natural and synthetic compounds attractive to Ae. aegypti larvae should be incorporated into integrated pest management programs through the use of baited traps or by improving the efficacy of larvicides commonly used in control campaigns.

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In mosquitoes, location of suitable sites for oviposition requires a set of visual, tactile, and olfactory cues that influences females before laying their eggs. The ability of gravid females to distinguish among potential oviposition sites that will or will not support the growth, development, and survival of their progeny is critical. Aedes aegypti (L.) and Aedes albopictus (Skuse) share ecological niches, being highly competitive in larval stage. We studied the oviposition behavior of both species in the presence of larvae of one or the other species (heterospecific or conspecific larvae). The number of eggs laid by gravid females on oviposition sites (water with different or the same species of Aedes larvae) were compared. The presence and density of heterospecific or conspecific larvae had a positive or negative effect on the ovipositional responses, measured as an oviposition activity index. For both species, the oviposition was not affected by heterospecific larvae with densities between 10 and 100 larvae in water, but a strong attractant behavior was observed for a density of 500 larvae in water. For Ae. albopictus in the presence of larvae of the same species (conspecific oviposition), we observed an attractant effect for larvae density of 10 but not for 100 or 500 larvae in water. Instead, for Ae. aegypti, we observed attraction only for 100 larvae, not for 10 or 500 larvae. Results presented here provide an additional insight about oviposition behavior responses of gravid females in the presence of conspecific and heterospecific larvae in breeding sites.

Aedes aegypti (L.) and Aedes albopictus (Skuse) (Diptera: Culicidae) are highly anthropophilic mosquito species and potential vectors of dengue and yellow fever. The location of suitable sites for oviposition requires a set of visual, tactile, and olfactory cues that influence females before they lay their eggs. In this study, the effect of n-heneicosane, a recognized oviposition pheromone of Ae. aegypti, on the olfactory receptors of the antennae of Ae. aegypti and Ae. albopictus was studied using electroantennographic detection coupled to gas chromatography (GC-EAD). A significant electroantennographic response to n-heneicosane in adult females of both mosquito species was observed. In addition, gravid Ae. albopictus females laid more eggs in substrate treated with n-heneicosane at 0.1, 1, or 10 p.p.m. than in the control, denoting oviposition attractancy. Conversely, at 30, 50, 100, and 200 p.p.m., more eggs were laid in the control substrate, indicating oviposition repellency. Analysis of the larval cuticle by GC and mass spectrometry confirmed the presence of n-heneicosane in the cuticles of Ae. albopictus larvae. The species-specific role of n-heneicosane as an oviposition pheromone in Ae. aegypti and its significance as a behaviour modifier of Ae. albopictus in breeding sites is discussed.