{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:08:21Z","timestamp":1770329301119,"version":"3.49.0"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico\u2013informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, \u201cAdrenergic receptor antagonist\u201d, \u201cATPase inhibitor\u201d, \u201cNF-kB pathway inhibitor\u201d and \u201cSerotonin receptor antagonist\u201d, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.<\/jats:p>","DOI":"10.3390\/v13081540","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T21:45:06Z","timestamp":1628113506000},"page":"1540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Beatriz","family":"Sierra","sequence":"first","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3988-3280","authenticated-orcid":false,"given":"Ana Cristina","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Daniel","family":"Soares","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Bruno","family":"Cavadas","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Ana B.","family":"Perez","sequence":"additional","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]},{"given":"Mayling","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]},{"given":"Eglis","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]},{"given":"Claudia","family":"Bracho","sequence":"additional","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4271-1527","authenticated-orcid":false,"given":"Luisa","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Maria G.","family":"Guzman","sequence":"additional","affiliation":[{"name":"Virology Department, PAHO\/WHO Collaborating Center for the Study of Dengue and its Vector, Pedro Kour\u00ed Institute of Tropical Medicine (IPK), Havana 11400, Cuba"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16055","DOI":"10.1038\/nrdp.2016.55","article-title":"Dengue infection","volume":"2","author":"Guzman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.actatropica.2016.11.020","article-title":"The emergence of arthropod-borne viral diseases: A global prospective on dengue, chikungunya and zika fevers","volume":"166","author":"Mayer","year":"2017","journal-title":"Acta Trop."},{"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","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S1473-3099(16)00146-8","article-title":"The global economic burden of dengue: A systematic analysis","volume":"16","author":"Shepard","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e08347","DOI":"10.7554\/eLife.08347","article-title":"The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus","volume":"4","author":"Kraemer","year":"2015","journal-title":"Elife"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1473-3099(10)70166-3","article-title":"Intrinsic antibody-dependent enhancement of microbial infection in macrophages: Disease regulation by immune complexes","volume":"10","author":"Halstead","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"647","DOI":"10.2217\/fvl-2018-0073","article-title":"Host ancestry and dengue fever: From mapping of candidate genes to prediction of worldwide genetic risk","volume":"13","author":"Oliveira","year":"2018","journal-title":"Future Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/ng.960","article-title":"Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1","volume":"43","author":"Khor","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sierra, B., Triska, P., Soares, P., Garcia, G., Perez, A.B., Aguirre, E., and Oliveira, M. (2017). OSBPL10, RXRA and lipid metabolism confer African-ancestry protection against dengue haemorrhagic fever in admixed Cubans. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006220"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Oliveira, M., Lert-Itthiporn, W., Cavadas, B., Fernandes, V., Chuansumrit, A., Anuncia\u00e7\u00e3o, O., Casademont, I., Koeth, F., Penova, M., and Tangnararatchakit, K. (2018). Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006202"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.meegid.2018.04.018","article-title":"Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease","volume":"62","author":"Oliveira","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"774","DOI":"10.4269\/ajtmh.2010.10-0090","article-title":"Liver involvement associated with dengue infection in adults in Vietnam","volume":"83","author":"Trung","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.12998\/wjcc.v3.i2.125","article-title":"Dengue and its effects on liver","volume":"3","author":"Samanta","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"de Silva, W.T., and Gunasekera, M. (2015). Spontaneous splenic rupture during the recovery phase of dengue fever. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1234-5"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nascimento, E.J., Braga-Neto, U., Calzavara-Silva, C.E., Gomes, A.L., Abath, F.G., Brito, C.A., Cordeiro, M.T., Silva, A.M., Magalh\u00e3es, C., and Andrade, R. (2009). Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007892"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Loke, P., Hammond, S.N., Leung, J.M., Kim, C.C., Batra, S., Rocha, C., Balmaseda, A., and Harris, E. (2010). Gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000710"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Popper, S.J., Gordon, A., Liu, M., Balmaseda, A., Harris, E., and Relman, D.A. (2012). Temporal dynamics of the transcriptional response to dengue virus infection in Nicaraguan children. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001966"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sessions, O.M., Tan, Y., Goh, K.C., Liu, Y., Tan, P., Rozen, S., and Ooi, E.E. (2013). Host cell transcriptome profile during wild-type and attenuated dengue virus infection. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002107"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.chom.2014.06.001","article-title":"Dengue virus infection induces expansion of a CD14(+)CD16(+) monocyte population that stimulates plasmablast differentiation","volume":"16","author":"Kwissa","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1086\/596507","article-title":"Patterns of gene transcript abundance in the blood of children with severe or uncomplicated dengue highlight differences in disease evolution and host response to dengue virus infection","volume":"199","author":"Long","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2147\/IDR.S22613","article-title":"Treatment of dengue fever","volume":"5","author":"Rajapakse","year":"2012","journal-title":"Infect Drug Resist."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000321892","article-title":"Statins reduce dengue virus production via decreased virion assembly","volume":"54","author":"Castellanos","year":"2011","journal-title":"Intervirology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Martinez-Gutierrez, M., Correa-Londo\u00f1o, L.A., Castellanos, J.E., Gallego-G\u00f3mez, J.C., and Osorio, J.E. (2014). Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087412"},{"key":"ref_24","first-page":"468","article-title":"Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"62","author":"Whitehorn","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17147","DOI":"10.1038\/s41598-018-35334-2","article-title":"Hyperlipidemia, statin use and dengue severity","volume":"8","author":"Chia","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/S0140-6736(19)32525-5","article-title":"Vaccine-attributable severe dengue in the Philippines","volume":"394","author":"Flasche","year":"2019","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nrd2265","article-title":"High-throughput electronic biology: Mining information for drug discovery","volume":"6","author":"Loging","year":"2007","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1126\/science.abe9403","article-title":"Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms","volume":"370","author":"Gordon","year":"2020","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The Connectivity Map: Using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles","volume":"171","author":"Subramanian","year":"2017","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/msb.145122","article-title":"Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling","volume":"10","author":"Agren","year":"2014","journal-title":"Mol. Syst. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6352","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41598-018-36636-1","article-title":"Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses","volume":"9","author":"Amemiya","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1128\/jcm.30.3.545-551.1992","article-title":"Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction","volume":"30","author":"Lanciotti","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Santiago, G.A., Vergne, E., Quiles, Y., Cosme, J., Vazquez, J., Medina, J.F., Medina, F., Col\u00f3n, C., Margolis, H., and Mu\u00f1oz-Jord\u00e1n, J.L. (2013). Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/annotation\/ae27d48b-025f-47ce-8427-4af59f821ad7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_37","first-page":"D991-995","article-title":"NCBI GEO: Archive for functional genomics data sets--update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e32942","DOI":"10.7554\/eLife.32942","article-title":"Single-cell transcriptional dynamics of flavivirus infection","volume":"7","author":"Zanini","year":"2018","journal-title":"Elife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"PubChem 2019 update: Improved access to chemical data","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: A major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s10561-016-9555-8","article-title":"Characterization of RNA isolated from eighteen different human tissues: Results from a rapid human autopsy program","volume":"17","author":"Walker","year":"2016","journal-title":"Cell Tissue Bank"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1159\/000318531","article-title":"Vasopressin and its immune effects in septic shock","volume":"2","author":"Russell","year":"2010","journal-title":"J. Innate Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nri2303","article-title":"Immunobiology of the TAM receptors","volume":"8","author":"Lemke","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e00553-15","DOI":"10.1128\/mBio.00553-15","article-title":"Dengue Virus NS Proteins Inhibit RIG-I\/MAVS Signaling by Blocking TBK1\/IRF3 Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating Virulence Determinant","volume":"6","author":"Dalrymple","year":"2015","journal-title":"MBio"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.4049\/jimmunol.2000411","article-title":"Dengue Virus Degrades USP33-ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells","volume":"205","author":"Mishra","year":"2020","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3727\/105221610X12819686555015","article-title":"ATF3, a hub of the cellular adaptive-response network, in the pathogenesis of diseases: Is modulation of inflammation a unifying component?","volume":"15","author":"Hai","year":"2010","journal-title":"Gene. Expr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/jmv.20195","article-title":"Internalization of the dengue virus is cell cycle modulated in HepG2, but not Vero cells","volume":"74","author":"Phoolcharoen","year":"2004","journal-title":"J. Med. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.virol.2019.11.015","article-title":"Novel anti-flavivirus drugs targeting the nucleolar distribution of core protein","volume":"541","author":"Tokunaga","year":"2020","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/viro.2002.1685","article-title":"Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA","volume":"304","author":"Diamond","year":"2002","journal-title":"Virology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1681\/ASN.2006070727","article-title":"Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway","volume":"18","author":"He","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Machado, C.R., Machado, E.S., Rohloff, R.D., Azevedo, M., Campos, D.P., de Oliveira, R.B., and Brasil, P. (2013). Is pregnancy associated with severe dengue? A review of data from the Rio de Janeiro surveillance information system. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002217"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.1038\/s41598-018-22639-5","article-title":"Hsp90 interacts with multiple dengue virus 2 proteins","volume":"8","author":"Srisutthisamphan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0092-8674(00)00015-5","article-title":"Functional discovery via a compendium of expression profiles","volume":"102","author":"Hughes","year":"2000","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41467-017-02772-x","article-title":"The effects of death and post-mortem cold ischemia on human tissue transcriptomes","volume":"9","author":"Ferreira","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"274025","DOI":"10.1155\/2015\/274025","article-title":"Dengue Virus Infection Causes the Activation of Distinct NF-\u03baB Pathways for Inducible Nitric Oxide Synthase and TNF-\u03b1 Expression in RAW264.7 Cells","volume":"2015","author":"Cheng","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.chom.2016.07.004","article-title":"A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection","volume":"20","author":"Barrows","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mazzon, M., Ortega-Prieto, A.M., Imrie, D., Luft, C., Hess, L., Czieso, S., Grove, J., Skelton, J.K., Farleigh, L., and Bugert, J.J. (2019). Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry. Viruses, 11.","DOI":"10.3390\/v11020176"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ejphar.2006.10.002","article-title":"Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells","volume":"555","author":"Ko","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Dai, J.P., Li, W.Z., Zhao, X.F., Wang, G.F., Yang, J.C., Zhang, L., Chen, X.X., Xu, Y.X., and Li, K.S. (2012). A drug screening method based on the autophagy pathway and studies of the mechanism of evodiamine against influenza A virus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042706"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.21873\/invivo.12221","article-title":"Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy","volume":"34","author":"Pollard","year":"2020","journal-title":"In Vivo"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1128\/JVI.00365-14","article-title":"Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling","volume":"88","author":"Smith","year":"2014","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12943-019-1127-7","article-title":"Role of HDACs in normal and malignant hematopoiesis","volume":"19","author":"Wang","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Delgado, F.G., C\u00e1rdenas, P., and Castellanos, J.E. (2018). Valproic Acid Downregulates Cytokine Expression in Human Macrophages Infected with Dengue Virus. Diseases, 6.","DOI":"10.3390\/diseases6030059"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Choy, M.M., Zhang, S.L., Costa, V.V., Tan, H.C., Horrevorts, S., and Ooi, E.E. (2015). Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004058"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/hep.26763","article-title":"Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and fibrosis","volume":"59","author":"Mukhopadhyay","year":"2014","journal-title":"Hepatology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:40:37Z","timestamp":1760164837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,4]]},"references-count":68,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081540"],"URL":"https:\/\/doi.org\/10.3390\/v13081540","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,4]]}}}