{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:08Z","timestamp":1786977008671,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arch Insect Biochem Physiol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The mosquito\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    is a primary vector responsible for transmitting major arboviruses, including dengue, Zika, chikungunya, and yellow fever. Increasing resistance to conventional synthetic insecticides, combined with their well\u2010known environmental drawbacks, underscores the urgent need for more selective, sustainable, and effective strategies for vector control. Chalcones have been previously identified by our research group as a promising chemical class of larvicidal agents, with preliminary evidence for distinct mechanisms of action. More recently, an additional strategy for integrated control of\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    in its adult stage has emerged through the inhibition of blood feeding, particularly via agonism of neuropeptide Y\u2010like receptor 7 (NPYLR7). In this context, this multi\u2010pronged investigation was conceived as a stage\u2010specific discovery framework addressing distinct biological vulnerabilities of\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    . Specifically, the study aimed to: evaluate the larvicidal potential of chalcones through integrated in silico and in vivo approaches targeting juvenile hormone transport; apply deep learning\u2013based high\u2010throughput virtual screening (HTVS) as a candidate\u2010prioritization strategy for identifying chemically plausible NPYLR7 agonists associated with blood\u2010feeding inhibition; and finally generate novel NPYLR7\u2010oriented molecular scaffolds using DeSAO (\u201cde novo drugs using Simulated Annealing Optimization)\u201d algorithm as a hypothesis\u2010generating de novo design methodology. These strategies were intentionally pursued as complementary, rather than convergent, discovery axes reflecting the distinct biological requirements of larval and adult mosquito control. Initially, a classical docking\u2010based virtual screening of 1070 chalcones from the PubChem database was conducted on the\n                    <jats:italic>A. aegypti<\/jats:italic>\n                    juvenile hormone\u2010binding protein (mJHBP), a hemolymph\u2010circulating protein involved in hormonal regulation of larval and adult development. Docking calculations revealed several analogues with favorable predicted binding energies. Three halogenated chalcones were then commercially acquired for experimental larvicidal assays, which identified 4\u2032\u2010chloro\u20104\u2010methoxychalcone (2c) as the most active compound after 72\u2009h exposure. In parallel, the Machine Learning driven HTVS and the DeSAO workflow independently identified and prioritized novel molecular scaffolds with predicted NPYLR7 agonist activity, generating chemically plausible candidates for subsequent experimental evaluation of blood\u2010meal inhibition in adult mosquitoes. Collectively, the results indicate that halogenated chalcones with moderately sized substituents may serve as promising larvicidal candidates, while HTVS and DeSAO provide complementary, chemically diverse architectures for future evaluation in blood\u2010meal control assays. Taken together, these findings reinforce the value of integrating computational, Machine Learning, and experimental methodologies within a unified pipeline, enabling both validated larvicidal discovery and biologically grounded candidate prioritization for adult mosquito control.\n                  <\/jats:p>","DOI":"10.1002\/arch.70138","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:29:31Z","timestamp":1773008971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated In Silico, In Vivo, and Deep Learning Approaches in the Discovery of Novel Candidate Molecules for\n                    <i>Aedes aegypti<\/i>\n                    Control"],"prefix":"10.1002","volume":"121","author":[{"given":"Herbert Bezerra","family":"Leite","sequence":"first","affiliation":[{"name":"Federal University of Vale do S\u00e3o Francisco Petrolina Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipe Alves Ribeiro","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering Federal University of Vale do S\u00e3o Francisco Juazeiro Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Beatriz Rocha","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Vale do S\u00e3o Francisco Petrolina Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3403-245X","authenticated-orcid":false,"given":"Vanessa Costa","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Vale do S\u00e3o Francisco Petrolina Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-5539","authenticated-orcid":false,"given":"Rosalvo F.","family":"Oliveira Neto","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering Federal University of Vale do S\u00e3o Francisco Juazeiro Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-0114","authenticated-orcid":false,"given":"Edilson B.","family":"Alencar Filho","sequence":"additional","affiliation":[{"name":"Federal University of Vale do S\u00e3o Francisco Petrolina Pernambuco Brazil"},{"name":"Department of Pharmaceutical Sciences Federal University of Vale do S\u00e3o Francisco Petrolina Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28083641"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/minf.202300167"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid3102.240754"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_6_1","unstructured":"BIOVIA. Dassault Syst\u00e8mes. Discovery Studio Modeling Environment Release 2021. San Diego CA: Dassault Syst\u00e8mes. 2021."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.041"},{"key":"e_1_2_8_8_1","unstructured":"European Centre for Disease Prevention and Control. (ECDC). 2023.Aedes aegypti\u2014Factsheet for Experts. Stockholm: ECDC accessed 20 October 2025.https:\/\/www.ecdc.europa.eu\/en\/disease-vectors\/facts\/mosquito-factsheets\/aedes-aegypti."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2000000200003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00390"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-120811-153700"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1615423114"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.802009"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.220.4598.671"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/insects11120858"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eswa.2025.127099"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2021.101178"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_8_20_1","unstructured":"S\u00e1 F. H. A.Triagem virtual na busca de potenciais agentes para o controle deAedes aegypti. MSc dissertation. Petrolina Brazil: Universidade Federal do Vale do S\u00e3o Francisco (UNIVASF). 92 p. 2022.https:\/\/portais.univasf.edu.br\/ppgcsb\/pesquisa\/dissertacoes-2022-1\/fernanda-hohana-almeida-e-sa-t-2020.pdf."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2022.106791"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.9b00325"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1132"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-024-06347-w"}],"container-title":["Archives of Insect Biochemistry and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/arch.70138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/arch.70138","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/arch.70138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:06:57Z","timestamp":1773029217000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/arch.70138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/arch.70138"],"URL":"https:\/\/doi.org\/10.1002\/arch.70138","archive":["Portico"],"relation":{},"ISSN":["0739-4462","1520-6327"],"issn-type":[{"value":"0739-4462","type":"print"},{"value":"1520-6327","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70138"}}