{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:46:39Z","timestamp":1790959599920,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Arboviruses such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) remain major global health threats, especially in tropical regions, with no effective antiviral treatments available. Recent research highlights progress in identifying antiviral compounds from natural sources against arboviruses belonging to the flavivirus genus, such as DENV and ZIKV. These compounds, derived from plants, marine organisms, and microorganisms, fall into several key chemical classes: quinones, flavonoids, phenolics, terpenoids, and alkaloids. Quinones inhibit viral entry and replication by targeting envelope proteins and proteases. Flavonoids disrupt RNA synthesis and show virucidal activity. Phenolic compounds reduce expression of non-structural proteins and inhibit enzyme function. Terpenoids demonstrate broad-spectrum activity against multiple arboviruses, while alkaloids interfere with early infection stages or viral enzymes. To support the reviewed literature, we performed molecular docking analyses of selected natural compounds and some arboviral proteins included as illustrative examples. These analyses support the structure\u2013activity relationships reported for some natural compounds and highlight their potential interactions with essential viral targets such as the NS2B-NS3 protease and NS5 polymerase. Together, these literature and computational insights highlight the potential of natural products as scaffolds for antiviral drug development.<\/jats:p>","DOI":"10.3390\/pathogens14111156","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:57:13Z","timestamp":1763038633000},"page":"1156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antiviral Compounds from Natural Sources Against Human Arboviruses: An Updated Review Including Illustrative In Silico Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Julio","family":"Aguiar-Pech","sequence":"first","affiliation":[{"name":"Unidad de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Cient\u00edfica de Yucat\u00e1n, Calle 43 N\u00famero 130 x 32 y 34, Merida 97205, Yucat\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-0031","authenticated-orcid":false,"given":"Roc\u00edo","family":"Borges-Arg\u00e1ez","sequence":"additional","affiliation":[{"name":"Unidad de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Cient\u00edfica de Yucat\u00e1n, Calle 43 N\u00famero 130 x 32 y 34, Merida 97205, Yucat\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3050-4480","authenticated-orcid":false,"given":"Henry","family":"Puerta-Guardo","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Centro de Investigaciones Regionales \u201cDr. Hideyo Noguchi\u201d, Universidad Aut\u00f3noma de Yucat\u00e1n (UADY), Merida 97225, Yucat\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/978-981-10-8727-1_19","article-title":"Roversi, Dengue and Zika: Control and Antiviral Treatment Strategies","volume":"1062","author":"Caputo","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1016\/j.vaccine.2020.04.011","article-title":"Arboviruses: A global public health threat","volume":"38","author":"Girard","year":"2020","journal-title":"Vaccine"},{"key":"ref_3","first-page":"988","article-title":"Molecular characteristics and replication mechanism of dengue, zika and chikungunya arboviruses, and their treatments with natural extracts from plants: An updated review","volume":"18","author":"Rodriguez","year":"2019","journal-title":"EXCLI J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11908-025-00862-2","article-title":"A New Emerging Threat","volume":"27","author":"Labiod","year":"2025","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, Q., and Kang, C. (2022). Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins. Membranes, 12.","DOI":"10.3390\/membranes12020231"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.antiviral.2013.03.008","article-title":"The flavivirus NS1 protein: Molecular and structural biology, immunology, role inpathogenesis and application asadiagnostic biomarker","volume":"98","author":"Muller","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-virology-101416-041848","article-title":"The good, the bad, and the shocking: The multiple roles of dengue virus nonstructural protein 1 in protection and pathogenesis","volume":"5","author":"Glasner","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41541-023-00658-2","article-title":"Is new dengue vaccine efficacy data a relief or cause for concern?","volume":"8","author":"Thomas","year":"2023","journal-title":"Npj Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1056\/NEJMe2314240","article-title":"Three Dengue Vaccines\u2014What Now?","volume":"390","author":"Halstead","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Obi, J.O., Guti, H., and Chua, J.V. (2021). Current Trends and Limitations in Dengue Antiviral Research. Trop. Med. Infect. Dis., 6.","DOI":"10.20944\/preprints202108.0364.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/14712598.2022.2151837","article-title":"Biologics for dengue prevention: Up-to-date","volume":"1","author":"Waickman","year":"2023","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liyanage, N.M., Nagahawatta, D.P., Jayawardena, T.U., Sanjeewa, K.K.A., Jayawrdhana, H.H.A.C.K., Kim, J.I., and Jeon, Y.J. (2023). Sulfated Polysaccharides from Seaweeds: A Promising Strategy for Combatting Viral Diseases\u2014A Review. Mar. Drugs, 21.","DOI":"10.3390\/md21090461"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ejmech.2017.03.005","article-title":"Prodrugs of triterpenoids and their derivatives","volume":"131","author":"Zhou","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e02013-25","DOI":"10.1128\/mbio.02013-25","article-title":"AntiviralDB: An expert-curated database of antiviral agents against human infectious diseases","volume":"16","author":"Huang","year":"2025","journal-title":"MBio"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1590\/S0074-02762013000500010","article-title":"Chloroquine use improves dengue-related symptoms","volume":"108","author":"Borges","year":"2013","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"282734","DOI":"10.1155\/2013\/282734","article-title":"Chloroquine inhibits dengue virus type 2 replication in vero cells but not in C6\/36 cells","volume":"2013","author":"Farias","year":"2013","journal-title":"Sci. World J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coph.2016.06.002","article-title":"Towards antiviral therapies for treating dengue virus infections","volume":"30","author":"Kaptein","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sung, C., Wei, Y., Watanabe, S., Lee, H.S., Khoo, Y.M., Fan, L., Rathore, A.P.S., Chan, K.W.K., Choy, M.M., and Kamaraj, U.S. (2016). Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004851"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S1473-3099(14)70730-3","article-title":"Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): A phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial","volume":"14","author":"Low","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.antiviral.2015.12.008","article-title":"Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy","volume":"127","author":"Watanabe","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sayce, A.C., Alonzi, D.S., Killingbeck, S.S., Tyrrell, B.E., Hill, M.L., Caputo, A.T., Iwaki, R., Kinami, K., Ide, D., and Kiappes, J.L. (2016). Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases\u2014Not Glycolipid Processing Enzymes. PLoS Neglected Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004524"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1021\/cr0004409","article-title":"Carbohydrate-based mimetics in drug design: Sugar amino acids and carbohydrate scaffolds","volume":"102","author":"Gruner","year":"2002","journal-title":"Chem. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Warfield, K.L., Schaaf, K.R., DeWald, L.E., Spurgers, K.B., Wang, W., Stavale, E., Mendenhall, M., Shilts, M.H., Stockwell, T.B., and Barnard, D.L. (2019). Lack of selective resistance of influenza A virus in presence of host-targeted antiviral, UV-4B. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43030-y"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Franco, E.J., de Mello, C.P.P., and Brown, A.N. (2021). Antiviral evaluation of UV-4B and interferon-alpha combination regimens against dengue virus. Viruses, 13.","DOI":"10.3390\/v13050771"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2016.03.001","article-title":"Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4","volume":"129","author":"Warfield","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12985-022-01751-z","article-title":"Searching for plant-derived antivirals against dengue virus and Zika virus","volume":"19","author":"Alves","year":"2022","journal-title":"Virol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1080\/10286020.2020.1779707","article-title":"Anthraquinone analogues with inhibitory activities against influenza a virus from Polygonatum odoratum","volume":"23","author":"Pang","year":"2021","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s11101-011-9209-1","article-title":"The chemical and biological activities of quinones: Overview and implications in analytical detection","volume":"10","author":"Ketola","year":"2011","journal-title":"Phytochem. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35806","DOI":"10.1039\/D1RA05686G","article-title":"Journey of anthraquinones as anticancer agents-a systematic review of recent literature","volume":"11","author":"Malik","year":"2021","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shao, Q., Liu, T., Wang, W., Liu, T., Jin, X., and Chen, Z. (2022). Promising Role of Emodin as Therapeutics to Against Viral Infections. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.902626"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Batista, M.N., Braga, A.C.S., Campos, G.R.F., Souza, M.M., de Matos, R.P.A., Lopes, T.Z., Candido, N.M., Lima, M.L.D., Machado, F.C., and de Andrade, S.T.Q. (2019). Natural products isolated from oriental medicinal herbs inactivate zika virus. Viruses, 11.","DOI":"10.3390\/v11010049"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8151","DOI":"10.3390\/molecules19068151","article-title":"Natural products as source of potential dengue antivirals","volume":"19","author":"Teixeira","year":"2014","journal-title":"Molecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.antiviral.2015.03.010","article-title":"Antiviral activities of 15 dengue NS2B-NS3 protease inhibitors using a human cell-based viral quantification assay","volume":"118","author":"Chu","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.antiviral.2010.12.006","article-title":"Anthracene-based Inhibitors of Dengue Virus NS2B-NS3 Protease","volume":"89","author":"Tomlinson","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Roa-Linares, V.C., Miranda-Brand, Y., Tangarife-Casta\u00f1o, V., Ochoa, R., Garc\u00eda, P.A., Castro, M.\u00c1., Betancur-Galvis, L., and Feliciano, A.S. (2019). Anti-herpetic, anti-dengue and antineoplastic activities of simple and heterocycle-fused derivatives of terpenyl-1,4-naphthoquinone and 1,4-anthraquinone. Molecules, 24.","DOI":"10.3390\/molecules24071279"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8701","DOI":"10.1080\/07391102.2023.2248262","article-title":"Computational evaluation of quinones of Nigella sativa L. as potential inhibitor of dengue virus NS5 methyltransferase","volume":"42","author":"Roney","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Da Costa, E.C.B., Amorim, R., Da Silva, F.C., Rocha, D.R., Papa, M.P., De Arruda, L.B., Mohana-Borges, R., Ferreira, V.F., Tanuri, A., and Da Costa, L.J. (2013). Synthetic 1,4-pyran naphthoquinones are potent inhibitors of dengue virus replication. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082504"},{"key":"ref_38","first-page":"1697","article-title":"Inhibition of Zika virus replication by synthetic bis-naphthoquinones","volume":"30","author":"Gonzaga","year":"2019","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"115620","DOI":"10.1016\/j.ejmech.2023.115620","article-title":"Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents","volume":"258","author":"Zhu","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/(SICI)1099-1573(200003)14:2<89::AID-PTR569>3.0.CO;2-C","article-title":"Antiviral effect of flavonoids on the dengue virus","volume":"14","author":"Taboada","year":"2000","journal-title":"Phyther. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1745-4514.2010.00514.x","article-title":"The inhibitory actions of houttuynia cordata aqueous extract on dengue virus and dengue-infected cells","volume":"36","author":"Leardkamolkarn","year":"2012","journal-title":"J. Food Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1186\/1743-422X-8-560","article-title":"Antiviral activity of four types of bioflavonoid against dengue virus type-2","volume":"8","author":"Zandi","year":"2011","journal-title":"Virol. J."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zandi, K., Teoh, B.T., Sam, S.S., Wong, P.F., Mustafa, M.R., and AbuBakar, S. (2012). Novel antiviral activity of baicalein against dengue virus. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-214"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104954","DOI":"10.1016\/j.antiviral.2020.104954","article-title":"Betulinic acid exhibits antiviral effects against dengue virus infection","volume":"184","author":"Loe","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.phytochem.2012.07.023","article-title":"Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri","volume":"84","author":"Allard","year":"2012","journal-title":"Phytochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1021\/acs.jnatprod.2c00464","article-title":"Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids","volume":"85","author":"Brand","year":"2022","journal-title":"J. Nat. Prod."},{"key":"ref_47","first-page":"260","article-title":"Studies on Quercus Iusitanica extracts on DENV-2 replication","volume":"30","author":"Rahman","year":"2006","journal-title":"Dengue Bull."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4172\/jaa.1000009","article-title":"Antiviral Activity of Emetine Dihydrochloride Against Dengue Virus Infection","volume":"1","author":"Low","year":"2009","journal-title":"J. Antivir. Antiretrovir."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s00705-010-0702-4","article-title":"Identification of palmatine as an inhibitor of West Nile virus","volume":"155","author":"Jia","year":"2010","journal-title":"Arch. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cataneo, A.H.D., \u00c1vila, E.P., de Oliveira Mendes, L.A., de Oliveira, V.G., Ferraz, C.R., de Almeida, M.V., Frabasile, S., Santos, C.N.D.D., Verri, W.A., and Bordignon, J. (2021). Flavonoids as Molecules with Anti-Zika virus Activity. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.710359"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00705-018-4083-4","article-title":"Baicalein and baicalin as Zika virus inhibitors","volume":"164","author":"Oo","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dewick, P. (2002). Medicinal Natural Products: A Byosynthetic Approach, John Wiley & Sons Ltd.. [2nd ed.].","DOI":"10.1002\/0470846275"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Calvo, \u00c1., de Oya, N.J., Mart\u00edn-Acebes, M.A., Garcia-Moruno, E., and Saiz, J.C. (2017). Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses West Nile Virus, Zika Virus, and Dengue Virus. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01314"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/np300059n","article-title":"Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi","volume":"75","author":"Bourjot","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imu.2016.06.001","article-title":"Identification of bioflavonoid as fusion inhibitor of dengue virus using molecular docking approach","volume":"3","author":"Mir","year":"2016","journal-title":"Inform. Med. Unlocked"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"17","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/11\/1156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T13:19:14Z","timestamp":1763039954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/11\/1156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":57,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["pathogens14111156"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14111156","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]}}}