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Searching for new bioactive molecules to design insecticides is a complex process since pesticides should be highly selective, active against the vector, and bio-safe for humans. Aiming to find natural compounds for mosquito control, we evaluated the insecticidal activity of essential oils (EOs) from 20 American native plants against Aedes aegypti larvae using bioassay, biochemical, and in silico analyses. The highest larvicide activity was exhibited by EOs from Steiractinia aspera (LC50 = 42.4 µg/mL), Turnera diffusa (LC50 = 70.9 µg/mL), Piper aduncum (LC50 = 55.8 µg/mL), Lippia origanoides (chemotype thymol/carvacrol) (LC50 = 61.9 µg/mL), L. origanoides (chemotype carvacrol/thymol) (LC50 = 59.8 µg/mL), Hyptis dilatata (LC50 = 61.1 µg/mL), Elaphandra quinquenervis (LC50 = 61.1 µg/mL), and Calycolpus moritzianus (LC50 = 73.29 µg/mL) after 24 h. This biological activity may be related to the disruption of the electron transport chain through the mitochondrial protein complexes. We hypothesized that the observed EOs' effect is due to their major components, where computational approaches such as homology modeling and molecular docking may suggest the possible binding pose of secondary metabolites that inhibit the mitochondrial enzymes and acetylcholinesterase activity (AChE). Our results provided insights into the possible mechanism of action of EOs and their major compounds for new insecticide designs targeting the mitochondria and AChE activity in A. aegypti for effective and safe insecticide.

Although there are existing vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), new COVID-19 cases are increasing due to low immunization coverage and the emergence of new variants. For this reason, new drugs to treat and prevent severe COVID-19 are needed. Here, we provide four different FDA-approved drugs against SARS-CoV-2 proteins involved in the entry and replication process, aiming to identify potential drugs to treat COVID-19. We use the main protease (Mpro), the spike glycoprotein (S protein), and RNA-dependent RNA polymerase (RdRp) as protein targets for anti- SARS-CoV-2 drugs. In our constructed database, we selected different drugs against each target (Mpro, S protein, and RdRp) based on their common interactions with relevant residues involved in viral entry at the host cell and replication. Furthermore, their stability inside the binding pocket, as well as their predicted binding-free energy, allow us to provide new insight into the possible drug repurposing of viomycin (interacting with Mpro) due to its interactions with key residues, such as Asn 143, Glu 166, and Gln 189 at the same time as hesperidin (interacting with the S protein) is interacting with residues Tyr 449, Ser 494, and Thr 500, keeping inside the predicted binding pocket, as well as interacting with residues in different variants of concern. Finally, we also suggest nystatin and elvitegravir (interacting with RdRp) as possible drugs due to their stability within the predicted pocket along the simulation and their interaction with key residues, such as Asp 760, Asp 761, and Asp 618. Altogether our results provide new knowledge about the possible mechanism of the inhibition of viomycin, hesperidin, elvitegravir, and nystatin to inhibit the viral life cycle of SARS-CoV-2 and some of its variants of concern (VOC). Additionally, some iodide-based contrast agents were also found to bind the S protein strongly, i.e., iohexol (−58.99 Kcal/mol), iotrolan (−76.19 Kcal/mol), and ioxilan (−62.37 Kcal/mol). Despite the information we report here as the possible strong interaction between these contrast agents and the SARS-CoV-2′s S protein, Mpro, and RdRp, we believe that further investigation, including chemical modifications in their structures, are needed for COVID-19 treatment.

<p>Con el fin de contribuir al conocimiento<br />de su actividad a nivel celular, se evaluó el<br />mecanismo de acción del aceite esencial<br />de Eucalyptus citriodora (Fam. Myrtaceae)<br />sobre la bioenergética mitocondrial, su efecto<br />sobre la velocidad de consumo de oxígeno<br />de mitocondrias energizadas (estados 3 y<br />4) y su coeficiente de control respiratorio<br />(CCR). Además, se analizó la actividad<br />de los complejos de la cadena respiratoria<br />usando técnicas espectrofotométricas. Los<br />resultados obtenidos indican que el aceite<br />esencial de E. citriodora aumenta la velocidad<br />del consumo de oxígeno en los estados 3 y 4,<br />disminuye el CCR, desacopla la fosforilación<br />oxidativa, aumenta la actividad de la<br />citocromo c oxidasa y aumenta la actividad<br />ATPasa en mitocondrias íntegras, a partir<br />de la concentración de 10 μg/mL. Estos<br />resultados sugieren que el aceite esencial o<br />sus metabolitos afectan el funcionamiento<br />normal del transporte de electrones de la<br />cadena respiratoria y la síntesis de ATP</p>

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Controlling gene expression is an instrumental tool for biotechnology, as it enables the dissection of gene function, affording precise spatial–temporal resolution. To generate this control, binary transactivational systems have been used employing a modular activator consisting of a DNA binding domain(s) fused to activation domain(s). For fly genetics, many binary transactivational systems have been exploited in vivo; however, as the study of complex problems often requires multiple systems that can be used in parallel, there is a need to identify additional bipartite genetic systems. To expand this molecular genetic toolbox, we tested multiple bacterially derived binary transactivational systems in Drosophila melanogaster including the p‐CymR operon from Pseudomonas putida, PipR operon from Streptomyces coelicolor, TtgR operon from Pseudomonas putida and the VanR operon from Caulobacter crescentus. Our work provides the first characterization of these systems in an animal model in vivo. For each system, we demonstrate robust tissue‐specific spatial transactivation of reporter gene expression, enabling future studies to exploit these transactivational systems for molecular genetic studies.

Controlling gene expression is an instrumental tool for biotechnology, as it enables the dissection of gene function, affording precise spatial-temporal resolution. To generate this control, binary transactivational systems have been used employing a modular activator consisting of a DNA binding domain(s) fused to activation domain(s). For fly genetics, many binary transactivational systems have been exploited in vivo; however as the study of complex problems often requires multiple systems that can be used in parallel, there is a need to identify additional bipartite genetic systems. To expand this molecular genetic toolbox, we tested multiple bacterially-derived binary transactivational systems in Drosophila melanogaster including the p-CymR operon from Pseudomonas putida, PipR operon from Streptomyces coelicolor, TtgR operon from Pseudomonas putida, and the VanR operon from Caulobacter crescentus. Our work provides the first characterization of these systems in an animal model in vivo. For each system we demonstrate robust tissue-specific spatial transactivation of reporter gene expression, enabling future studies to exploit these transactivational systems for molecular genetic studies.