{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:14:19Z","timestamp":1791839659406,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001793","name":"Queensland University of Technology","doi-asserted-by":"publisher","award":["Intramural funding"],"award-info":[{"award-number":["Intramural funding"]}],"id":[{"id":"10.13039\/501100001793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dengue is an arboviral disease caused by dengue virus (DENV), leading to approximately 25,000 deaths\/year and with over 40% of the world\u2019s population at risk. Increased international travel and trade, poorly regulated urban expansion, and warming global temperatures have expanded the geographic range and incidence of the virus in recent decades. This study used phylogenetic and selection pressure analyses to investigate trends in DENV evolution, using whole genome coding sequences from publicly available databases alongside newly sequenced isolates collected between 1963\u20131997 from Southeast Asia and the Pacific. Results revealed very similar phylogenetic relationships when using the envelope gene and the whole genome coding sequences. Although DENV evolution is predominantly driven by negative selection, a number of amino acid sites undergoing positive selection were found across the genome, with the majority located in the envelope and NS5 genes. Some genotypes appear to be diversifying faster than others within each serotype. The results from this research improve our understanding of DENV evolution, with implications for disease control efforts such as Wolbachia-based biocontrol and vaccine design.<\/jats:p>","DOI":"10.3390\/v14040703","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:45:51Z","timestamp":1648590351000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Global Evolutionary History and Dynamics of Dengue Viruses Inferred from Whole Genome Sequences"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-201X","authenticated-orcid":false,"given":"Caleb J.","family":"Stica","sequence":"first","affiliation":[{"name":"Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, 300 Herston Road, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-665X","authenticated-orcid":false,"given":"Roberto A.","family":"Barrero","sequence":"additional","affiliation":[{"name":"eResearch Office, Division of Research and Innovation, Queensland University of Technology, P Block, 2 George Street, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4935-7794","authenticated-orcid":false,"given":"Rachael Z.","family":"Murray","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, KG-Q Block, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor J.","family":"Devine","sequence":"additional","affiliation":[{"name":"Mosquito Control Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"School of Biology and Environmental Science, Queensland University of Technology, R Block, 2 George Street, Brisbane, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8628-4216","authenticated-orcid":false,"given":"Francesca D.","family":"Frentiu","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, 300 Herston Road, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/eva.12554","article-title":"Challenges in dengue research: A computational perspective","volume":"11","author":"Lourenco","year":"2018","journal-title":"Evol. Appl."},{"key":"ref_2","unstructured":"(2020, April 20). Dengue and Sever Dengue Fact Sheet. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_4","unstructured":"(2021, March 26). Dengue. Available online: https:\/\/www.worldmosquitoprogram.org\/en\/learn\/mosquito-borne-diseases\/dengue#:~:text=Each%20year%2C%20an%20estimated%20390,That\u2019s%20each%20year."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e42496","DOI":"10.7554\/eLife.42496","article-title":"Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics","volume":"8","author":"Bell","year":"2019","journal-title":"eLife"},{"key":"ref_6","unstructured":"World Health Organization (2020, September 23). Global Strategy for Dengue Prevention and Control 2012\u20132020. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/75303."},{"key":"ref_7","unstructured":"Knipe, D.M., and Howley, P.M. (2013). Fields Virology, Wolters Kluwer\/Lippincott Williams & Wilkins Health. [6th ed.]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S0188-4409(02)00378-8","article-title":"The global emergence\/resurgence of arboviral diseases as public health problems","volume":"33","author":"Gubler","year":"2002","journal-title":"Arch. Med. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/s41564-019-0476-8","article-title":"The current and future global distribution and population at risk of dengue","volume":"4","author":"Messina","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_10","first-page":"2","article-title":"The History and Evolution of Human Dengue Emergence","volume":"72","author":"Maramorosch","year":"2008","journal-title":"Advances in Virus Research"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0042-6822(90)90102-W","article-title":"Molecular evolution and distribution of dengue viruses type 1 and 2 in nature","volume":"174","year":"1990","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14234","DOI":"10.1073\/pnas.0602768103","article-title":"Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok","volume":"103","author":"Adams","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nunes, M.R., Palacios, G., Faria, N.R., Sousa, E.C., Pantoja, J.A., Rodrigues, S.G., Carvalho, V.L., Medeiros, D.B., Savji, N., and Baele, G. (2014). Air travel is associated with intracontinental spread of dengue virus serotypes 1-3 in Brazil. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002769"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0966-842X(99)01669-8","article-title":"The causes and consequences of genetic variation in dengue virus","volume":"8","author":"Holmes","year":"2000","journal-title":"Trends Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1567-1348(03)00004-2","article-title":"The origin, emergence and evolutionary genetics of dengue virus","volume":"3","author":"Holmes","year":"2003","journal-title":"Infect. Genet. Evol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15259","DOI":"10.1073\/pnas.0507320102","article-title":"Dynamic effects of antibody-dependent enhancement on the fitness of viruses","volume":"102","author":"Cummings","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6785-8-1","article-title":"Superior infectivity for mosquito vectors contributes to competitive displacement among strains of dengue virus","volume":"8","author":"Hanley","year":"2008","journal-title":"BMC Ecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1128\/JVI.06458-11","article-title":"Dengue-1 virus clade replacement in Thailand associated with enhanced mosquito transmission","volume":"86","author":"Lambrechts","year":"2012","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13125","DOI":"10.1128\/JVI.01822-14","article-title":"Increased replicative fitness of a dengue virus 2 clade in native mosquitoes: Potential contribution to a clade replacement event in Nicaragua","volume":"88","author":"Quiner","year":"2014","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.meegid.2012.05.012","article-title":"Complex dynamic of dengue virus serotypes 2 and 3 in Cambodia following series of climate disasters","volume":"15","author":"Duong","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.meegid.2018.04.032","article-title":"Understanding dengue virus evolution to support epidemic surveillance and counter-measure development","volume":"62","author":"Pollett","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13910","DOI":"10.1073\/pnas.96.24.13910","article-title":"Mutation rates among RNA viruses","volume":"96","author":"Drake","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3389\/fmicb.2020.01371","article-title":"Application of Next-Generation Sequencing to Reveal How Evolutionary Dynamics of Viral Population Shape Dengue Epidemiology","volume":"11","author":"Ko","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1017\/S0950268816001990","article-title":"Occurrence of co-infection with dengue viruses during 2014 in New Delhi, India","volume":"145","author":"Tazeen","year":"2017","journal-title":"Epidemiol. Infect."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lequime, S., Fontaine, A., Ar Gouilh, M., Moltini-Conclois, I., and Lambrechts, L. (2016). Genetic Drift, Purifying Selection and Vector Genotype Shape Dengue Virus Intra-host Genetic Diversity in Mosquitoes. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006111"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1093\/molbev\/msg182","article-title":"Selection-driven evolution of emergent dengue virus","volume":"20","author":"Bennett","year":"2003","journal-title":"Mol. Biol. Evol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11296","DOI":"10.1128\/JVI.77.20.11296-11298.2003","article-title":"Patterns of intra- and interhost nonsynonymous variation reveal strong purifying selection in dengue virus","volume":"77","author":"Holmes","year":"2003","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.meegid.2011.12.011","article-title":"Comparative evolutionary epidemiology of dengue virus serotypes","volume":"12","author":"Costa","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ketkar, H., Herman, D., and Wang, P. (2019). Genetic Determinants of the Re-Emergence of Arboviral Diseases. Viruses, 11.","DOI":"10.3390\/v11020150"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00705-021-04973-8","article-title":"Molecular evolution of dengue virus types 1 and 4 in Korean travelers","volume":"166","author":"Hwang","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Guan, J., He, Z., Qin, M., Deng, X., Chen, J., Duan, S., Gao, X., Pan, Y., Chen, J., and Yang, Y. (2021). Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018. BMC Infect. Dis, 21.","DOI":"10.1186\/s12879-021-05823-3"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zangmo, S., Darnal, J.B., Gyeltshen, S., Thapa, B.T., Rodpradit, P., Chinnawirotpisan, P., Manasatienkij, W., Macareo, L.R., Fernandez, S., and Wangchuk, S. (2020). Molecular epidemiology of dengue fever outbreaks in Bhutan, 2016\u20132017. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008165"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sun, B., Zhang, X., Zhang, H., Liu, H., Sun, L., Tan, Q., Liang, M., Wu, D., and Liu, D. (2020). Genomic epidemiological characteristics of dengue fever in Guangdong province, China from 2013 to 2017. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008049"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Queiroz, J., Botelho-Souza, L.F., Nogueira-Lima, F.S., Rampazzo, R.C.P., Krieger, M.A., Zambenedetti, M.R., Marchini, F.K., Borghetti, I.A., Pereira, D.B., and Salcedo, J.M.V. (2020). Phylogenetic Characterization of Arboviruses in Patients Suffering from Acute Fever in Rond\u00f4nia, Brazil. Viruses, 12.","DOI":"10.3390\/v12080889"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Inizan, C., O\u2019Connor, O., Worwor, G., Cabemaiwai, T., Grignon, J.C., Girault, D., Minier, M., Prot, M., Ballan, V., and Pakoa, G.J. (2020). Molecular Characterization of Dengue Type 2 Outbreak in Pacific Islands Countries and Territories, 2017\u20132020. Viruses, 12.","DOI":"10.3390\/v12101081"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104391","DOI":"10.1016\/j.meegid.2020.104391","article-title":"Epidemiological implications of the genetic diversification of dengue virus (DENV) serotypes and genotypes in Mexico","volume":"84","author":"David","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","article-title":"Cd-hit: A fast program for clustering and comparing large sets of protein or nucleotide sequences","volume":"22","author":"Li","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: Accelerated for clustering the next-generation sequencing data","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"vev003","DOI":"10.1093\/ve\/vev003","article-title":"RDP4: Detection and analysis of recombination patterns in virus genomes","volume":"1","author":"Martin","year":"2015","journal-title":"Virus Evol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"vey016","DOI":"10.1093\/ve\/vey016","article-title":"Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10","volume":"4","author":"Suchard","year":"2018","journal-title":"Virus Evol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/molbev\/msi103","article-title":"Bayesian coalescent inference of past population dynamics from molecular sequences","volume":"22","author":"Drummond","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/sysbio\/syy032","article-title":"Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7","volume":"67","author":"Rambaut","year":"2018","journal-title":"Syst. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1006\/viro.2002.1686","article-title":"Diversity and evolution of the envelope gene of dengue virus type 1","volume":"303","author":"Goncalvez","year":"2002","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1006\/viro.2002.1447","article-title":"Phylogenetic relationships and differential selection pressures among genotypes of dengue-2 virus","volume":"298","author":"Twiddy","year":"2002","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1099\/0022-1317-75-1-65","article-title":"Molecular evolution and epidemiology of dengue-3 viruses","volume":"75","author":"Lanciotti","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1099\/0022-1317-78-9-2279","article-title":"Molecular evolution and phylogeny of dengue-4 viruses","volume":"78","author":"Lanciotti","year":"1997","journal-title":"J. Gen. Virol"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New algorithms and methods to estimate maximum-likelihood phylogenies: Assessing the performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1093\/molbev\/msx149","article-title":"SMS: Smart Model Selection in PhyML","volume":"34","author":"Lefort","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"vew007","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen)","volume":"2","author":"Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/molbev\/msz197","article-title":"HyPhy 2.5-A Customizable Platform for Evolutionary Hypothesis Testing Using Phylogenies","volume":"37","author":"Poon","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1093\/molbev\/msx335","article-title":"Datamonkey 2.0: A Modern Web Application for Characterizing Selective and Other Evolutionary Processes","volume":"35","author":"Weaver","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/molbev\/msi105","article-title":"Not so different after all: A comparison of methods for detecting amino acid sites under selection","volume":"22","author":"Frost","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1093\/molbev\/msv022","article-title":"Less is more: An adaptive branch-site random effects model for efficient detection of episodic diversifying selection","volume":"32","author":"Smith","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Murrell, B., Wertheim, J.O., Moola, S., Weighill, T., Scheffler, K., and Kosakovsky Pond, S.L. (2012). Detecting individual sites subject to episodic diversifying selection. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002764"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/molbev\/mst030","article-title":"FUBAR: A fast, unconstrained bayesian approximation for inferring selection","volume":"30","author":"Murrell","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3201\/eid2302.160751","article-title":"Genetic Diversity and New Lineages of Dengue Virus Serotypes 3 and 4 in Returning Travelers, Germany, 2006\u20132015","volume":"23","author":"Shihada","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.meegid.2011.12.005","article-title":"Population structure of the dengue viruses, Aragua, Venezuela, 2006\u20132007. Insights into dengue evolution under hyperendemic transmission","volume":"12","author":"Villegas","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1128\/JVI.02445-08","article-title":"Genomic epidemiology of a dengue virus epidemic in urban Singapore","volume":"83","author":"Schreiber","year":"2009","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.3201\/eid2212.160813","article-title":"Highly Divergent Dengue Virus Type 2 in Traveler Returning from Borneo to Australia","volume":"22","author":"Liu","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.tim.2013.12.011","article-title":"Global spread of dengue virus types: Mapping the 70 year history","volume":"22","author":"Messina","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nrmicro3570","article-title":"True Blood: Dengue virus evolution","volume":"13","author":"Wash","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1126\/science.abk0058","article-title":"Antigenic evolutin of dengue viruses over 20 years","volume":"374","author":"Katzelnick","year":"2021","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.mib.2008.06.004","article-title":"Structural proteomics of dengue virus","volume":"11","author":"Perera","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.2174\/1381612826666200523174753","article-title":"A Review on the Progress and Prospects of Dengue Drug Discovery Targeting NS5 RNA- Dependent RNA Polymerase","volume":"26","author":"Maddipati","year":"2020","journal-title":"Curr. Pharm. Des."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/703\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:18Z","timestamp":1760136318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/4\/703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":66,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["v14040703"],"URL":"https:\/\/doi.org\/10.3390\/v14040703","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]}}}