{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:10:24Z","timestamp":1790914224895,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SECIHTI","award":["CBF-2025-I-1331"],"award-info":[{"award-number":["CBF-2025-I-1331"]}]},{"name":"SECIHTI","award":["CVU 780737"],"award-info":[{"award-number":["CVU 780737"]}]},{"DOI":"10.13039\/501100005343","name":"FUNDACI\u00d3N IMSS","doi-asserted-by":"publisher","award":["R-2024-785-073"],"award-info":[{"award-number":["R-2024-785-073"]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>RNA viruses remain a significant public health concern due to their rapid evolution, genetic variability, and capacity to trigger recurrent epidemics and pandemics. Over the last decade, natural products have gained attention as a valuable source of antiviral candidates, offering structural diversity, accessibility, and favorable safety profiles. This review highlights key replication mechanisms of RNA viruses and their associated therapeutic targets, including RNA-dependent RNA polymerase, viral proteases, and structural proteins mediating entry and maturation. We summarize recent advances in the identification of bioactive compounds such as flavonoids, alkaloids, terpenes, lectins, and polysaccharides that exhibit inhibitory activity against clinically relevant pathogens, including the Influenza A virus (IAV), human immunodeficiency viruses (HIV), dengue virus (DENV), Zika virus (ZIKV), and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Special emphasis is placed on the integration of in silico screening, in vitro validation, and nanotechnology-based delivery systems that address challenges of stability, bioavailability, and specificity. Furthermore, the growing role of artificial intelligence, drug repurposing strategies, and curated antiviral databases is discussed as a means to accelerate therapeutic discovery. Despite persistent limitations in clinical translation and standardization, natural products represent a promising and sustainable platform for the development of next-generation antivirals against RNA viruses.<\/jats:p>","DOI":"10.3390\/biom15101467","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"1467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural Compounds with Antiviral Activity Against Clinically Relevant RNA Viruses: Advances of the Last Decade"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8050-4587","authenticated-orcid":false,"given":"David Mauricio","family":"Ca\u00f1edo-Figueroa","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"},{"name":"Faculty of Medicine, Autonomous University of Sinaloa, Culiacan 80246, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Nahomi","family":"Calder\u00f3n-Sandate","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-697X","authenticated-orcid":false,"given":"Jonathan","family":"Hern\u00e1ndez-Castillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"},{"name":"Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7846-6982","authenticated-orcid":false,"given":"Manuel Josafat","family":"Huerta-Garza","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1930-2685","authenticated-orcid":false,"given":"Ximena","family":"Hern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-8052","authenticated-orcid":false,"given":"Manuel Adri\u00e1n","family":"Vel\u00e1zquez-Cervantes","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Circuito Mario de La Cueva s\/n, C.U, Coyoac\u00e1n, Mexico City 04510, Mexico"},{"name":"Laboratorio de Biolog\u00eda Molecular, Centro Nacional de Referencia II Valle de M\u00e9xico, Salud Digna, Tlalnepantla de Baz 54075, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-0077","authenticated-orcid":false,"given":"Giovanna Berenice","family":"Barrera-Aveleida","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomembranas, Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-1201","authenticated-orcid":false,"given":"Juan Valentin","family":"Trujillo-Paez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flor Itzel","family":"Lira-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8790-2341","authenticated-orcid":false,"given":"Blanca Azucena","family":"Marquez-Reyna","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5726-5953","authenticated-orcid":false,"given":"Mois\u00e9s","family":"Le\u00f3n-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Perinatal y Dise\u00f1o Molecular de Ant\u00edgenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatolog\u00eda \u201cIsidro Espinosa de los Reyes\u201d, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina","family":"Garc\u00eda-Herrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-9812","authenticated-orcid":false,"given":"Juan Fidel","family":"Osuna-Ramos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Autonomous University of Sinaloa, Culiacan 80246, Mexico"},{"name":"Laboratorio de Virolog\u00eda y Dise\u00f1o de Antivirales, Facultad de Medicina, Universidad Aut\u00f3noma de Sinaloa (UAS), Culiacan 80246, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-6260","authenticated-orcid":false,"given":"Luis Adri\u00e1n","family":"De Jes\u00fas-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, 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(2023). Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19. Life, 13.","DOI":"10.3390\/life13030617"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/14712598.2020.1739643","article-title":"Current Advances in the Algae-Made Biopharmaceuticals Field","volume":"20","year":"2020","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5584\/jiomics.v14i3.234","article-title":"Computational Screening of Natural Compounds as Antiviral Candidates Targeting the SARS-CoV-2 Main Protease","volume":"14","author":"Zatla","year":"2024","journal-title":"J. Integr. Omics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s40203-020-00073-8","article-title":"Evaluation of Certain Medicinal Plants Compounds as New Potential Inhibitors of Novel Corona Virus (COVID-19) Using Molecular Docking Analysis","volume":"9","author":"Alrasheid","year":"2021","journal-title":"Silico Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1002\/ptr.7468","article-title":"The Effect of Curcumin on the Risk of Mortality in Patients with COVID-19: A Systematic Review and Meta-analysis of Randomized Trials","volume":"36","author":"Kow","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e06350","DOI":"10.1016\/j.heliyon.2021.e06350","article-title":"Antiviral and Immunomodulatory Activity of Curcumin: A Case for Prophylactic Therapy for COVID-19","volume":"7","author":"Thimmulappa","year":"2021","journal-title":"Heliyon"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Payne, S. (2017). Introduction to RNA Viruses. Viruses, 97\u2013105.","DOI":"10.1016\/B978-0-12-803109-4.00010-6"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/1389202916666150707160613","article-title":"RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load","volume":"16","author":"Poltronieri","year":"2015","journal-title":"Curr. Genom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1128\/br.35.3.235-241.1971","article-title":"Expression of Animal Virus Genomes","volume":"35","author":"Baltimore","year":"1971","journal-title":"Bacteriol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.virol.2015.02.039","article-title":"Origins and Evolution of Viruses of Eukaryotes: The Ultimate Modularity","volume":"479\u2013480","author":"Koonin","year":"2015","journal-title":"Virology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1543","DOI":"10.1002\/wrna.1543","article-title":"Viral Modulation of Cellular RNA Alternative Splicing: A New Key Player in Virus\u2013Host Interactions?","volume":"10","author":"Boudreault","year":"2019","journal-title":"WIREs RNA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0065-3527(06)66005-3","article-title":"The Molecular Biology of Coronaviruses","volume":"66","author":"Masters","year":"2006","journal-title":"Adv. Virus Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S0140-6736(14)60163-X","article-title":"Avian Influenza A H10N8\u2014A Virus on the Verge?","volume":"383","author":"Schmolke","year":"2014","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ng, T.I., Correia, I., Seagal, J., DeGoey, D.A., Schrimpf, M.R., Hardee, D.J., Noey, E.L., and Kati, W.M. (2022). Antiviral Drug Discovery for the Treatment of COVID-19 Infections. Viruses, 14.","DOI":"10.3390\/v14050961"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.virol.2015.02.031","article-title":"Molecular Biology of Hepatitis B Virus Infection","volume":"479\u2013480","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"242","DOI":"10.5501\/wjv.v12.i5.242","article-title":"Emerging Perspectives on RNA Virus-Mediated Infections: From Pathogenesis to Therapeutic Interventions","volume":"12","author":"Mohanty","year":"2023","journal-title":"World J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Deng, H., Cao, H., Wang, Y., Li, J., Dai, J., Li, L.-F., Qiu, H.-J., and Li, S. (2024). Viral Replication Organelles: The Highly Complex and Programmed Replication Machinery. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1450060"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tian, W.J., and Wang, X.J. (2023). Broad-Spectrum Antivirals Derived from Natural Products. Viruses, 15.","DOI":"10.3390\/v15051100"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Picarazzi, F., Vicenti, I., Saladini, F., Zazzi, M., and Mori, M. (2020). Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge. Molecules, 25.","DOI":"10.3390\/molecules25235695"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Melano, I., Lo, Y.C., and Su, W.C. (2023). Characterization of Host Substrates of SARS-CoV-2 Main Protease. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1251705"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Miczi, M., Golda, M., Kunkli, B., Nagy, T., T\u0151zs\u00e9r, J., and M\u00f3ty\u00e1n, J.A. (2020). Identification of Host Cellular Protein Substrates of SARS-CoV-2 Main Protease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249523"},{"key":"ref_22","first-page":"1597","article-title":"Crystal Structure of Unlinked NS2B-NS3 Protease from Zika Virus","volume":"354","author":"Zhang","year":"2016","journal-title":"Science (1979)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105516","DOI":"10.1016\/j.antiviral.2022.105516","article-title":"Flavivirus Proteases: The Viral Achilles Heel to Prevent Future Pandemics","volume":"210","author":"Teramoto","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s00705-021-05026-w","article-title":"Nuclear Localization of Non-Structural Protein 3 (NS3) during Dengue Virus Infection","volume":"166","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"108294","DOI":"10.1016\/j.isci.2023.108294","article-title":"An Ivermectin\u2014Atorvastatin Combination Impairs Nuclear Transport Inhibiting Dengue Infection in Vitro and in Vivo","volume":"26","year":"2023","journal-title":"iScience"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"De Jes\u00fas-Gonz\u00e1lez, L.A., Palacios-R\u00e1palo, S., Reyes-Ruiz, J.M., Osuna-Ramos, J.F., Cordero-Rivera, C.D., Farfan-Morales, C.N., Guti\u00e9rrez-Escolano, A.L., and Del \u00c1ngel, R.M. (2021). The Nuclear Pore Complex is a Key Target of Viral Proteases to Promote Viral Replication. Viruses, 13.","DOI":"10.3390\/v13040706"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01773-22","DOI":"10.1128\/jvi.01773-22","article-title":"Nucleo-Cytoplasmic Transport of ZIKV Non-Structural 3 Protein Is Mediated by Importin-\u03b1\/\u03b2 and Exportin CRM-1","volume":"97","author":"Cisneros","year":"2023","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"De Jes\u00fas-Gonz\u00e1lez, L.A., Cervantes-Salazar, M., Reyes-Ruiz, J.M., Osuna-Ramos, J.F., Farf\u00e1n-Morales, C.N., Palacios, S., P\u00e9rez-Olais, J.H., Rivera, C.D.C., Monz\u00f3n, A.M.H., and Ru\u00edz-Jim\u00e9nez, F. (2020). The Nuclear Pore Complex: A Target for NS3 Protease of Dengue and Zika Viruses. Viruses, 12.","DOI":"10.3390\/v12060583"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"jcs253237","DOI":"10.1242\/jcs.253237","article-title":"Picornavirus 3C\u2014A Protease Ensuring Virus Replication and Subverting Host Responses","volume":"134","author":"Yi","year":"2021","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2004.03.009","article-title":"Regulation of Semliki Forest Virus RNA Replication: A Model for the Control of Alphavirus Pathogenesis in Invertebrate Hosts","volume":"323","author":"Kim","year":"2004","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17717","DOI":"10.1073\/pnas.0508531102","article-title":"Hepatitis C Virus Protease NS3\/4A Cleaves Mitochondrial Antiviral Signaling Protein off the Mitochondria to Evade Innate Immunity","volume":"102","author":"Li","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mondal, S., Sarvari, G., and Boehr, D.D. (2023). Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA. Viruses, 15.","DOI":"10.3390\/v15122413"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41392-022-01039-2","article-title":"Molecular Characteristics, Immune Evasion, and Impact of SARS-CoV-2 Variants","volume":"7","author":"Sun","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lundin, A., Dijkman, R., Bergstr\u00f6m, T., Kann, N., Adamiak, B., Hannoun, C., Kindler, E., J\u00f3nsd\u00f3ttir, H.R., Muth, D., and Kint, J. (2014). Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004166"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.virol.2006.09.023","article-title":"Mda-5, but Not RIG-I, Is a Common Target for Paramyxovirus V Proteins","volume":"359","author":"Childs","year":"2007","journal-title":"Virology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/JVI.01768-08","article-title":"Mechanism of Mda-5 Inhibition by Paramyxovirus V Proteins","volume":"83","author":"Childs","year":"2009","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liu, Y., Olagnier, D., and Lin, R. (2017). Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00662"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1073\/pnas.1920631117","article-title":"HIV-1 Uncoats in the Nucleus near Sites of Integration","volume":"117","author":"Burdick","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.tim.2023.03.008","article-title":"Interplay between Endogenous and Exogenous Human Retroviruses","volume":"31","author":"Kyriakou","year":"2023","journal-title":"Trends Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.coph.2020.09.017","article-title":"Recent Discoveries in HIV-1 Reverse Transcriptase Inhibitors","volume":"54","author":"Gu","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S1572-5995(00)80051-4","article-title":"Natural Products as Antiviral Agents","volume":"24","year":"2000","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e10480","DOI":"10.7717\/peerj.10480","article-title":"Repurposing FDA-Approved Phytomedicines, Natural Products, Antivirals and Cell Protectives against SARS-CoV-2 (COVID-19) RNA-Dependent RNA Polymerase","volume":"8","author":"Kandeel","year":"2020","journal-title":"PeerJ"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.1021\/acs.jafc.1c02050","article-title":"Epigallocatechin Gallate Inhibits the Uridylate-Specific Endoribonuclease Nsp15 and Efficiently Neutralizes the SARS-CoV-2 Strain","volume":"69","author":"Hong","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18567","DOI":"10.7448\/IAS.16.1.18567","article-title":"Non-nucleoside Reverse Transcriptase Inhibitors: A Review on Pharmacokinetics, Pharmacodynamics, Safety and Tolerability","volume":"16","author":"Usach","year":"2013","journal-title":"J. Int. AIDS Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/cbdd.13770","article-title":"Novel Peptides with HIV-1 Reverse Transcriptase Inhibitory Activity Derived from the Fruits of Quercus Infectoria","volume":"97","author":"Seetaha","year":"2021","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105433","DOI":"10.1016\/j.antiviral.2022.105433","article-title":"In Vitro and in Vivo Antiviral Activity of Nucleoside Analogue CHPMPC against African Swine Fever Virus Replication","volume":"208","author":"Goulding","year":"2022","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8646","DOI":"10.1074\/jbc.M109.034926","article-title":"A Lectin Isolated from Bananas Is a Potent Inhibitor of HIV Replication","volume":"285","author":"Swanson","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/lam.13637","article-title":"Antiviral Plant-derived Natural Products to Combat RNA Viruses: Targets throughout the Viral Life Cycle","volume":"75","author":"Owen","year":"2022","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.cell.2015.09.056","article-title":"Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity","volume":"163","author":"Swanson","year":"2015","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.1074\/jbc.RA119.007360","article-title":"HIV-1 Anchor Inhibitors and Membrane Fusion Inhibitors Target Distinct but Overlapping Steps in Virus Entry","volume":"294","author":"Eggink","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Berillo, D., Yeskendir, A., Zharkinbekov, Z., Raziyeva, K., and Saparov, A. (2021). Peptide-Based Drug Delivery Systems. Medicina, 57.","DOI":"10.3390\/medicina57111209"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.str.2017.03.015","article-title":"The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans","volume":"25","author":"Hopper","year":"2017","journal-title":"Structure"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2016.07.011","article-title":"Middle East Respiratory Syndrome Coronavirus Infection Is Inhibited by Griffithsin","volume":"133","author":"Millet","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Colunga Biancatelli, R.M.L., Berrill, M., Catravas, J.D., and Marik, P.E. (2020). Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01451"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15371","DOI":"10.1021\/acs.jmedchem.0c01348","article-title":"Triterpenoid-Mediated Inhibition of Virus\u2013Host Interaction: Is Now the Time for Discovering Viral Entry\/Release Inhibitors from Nature?","volume":"63","author":"Li","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wu, W., Li, R., Li, X., He, J., Jiang, S., Liu, S., and Yang, J. (2015). Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses, 8.","DOI":"10.3390\/v8010006"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1002\/ddr.21815","article-title":"Potential Antiviral Activity of Isorhamnetin against SARS-CoV-2 Spike Pseudotyped Virus in Vitro","volume":"82","author":"Zhan","year":"2021","journal-title":"Drug Dev. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.apsb.2020.02.008","article-title":"Analysis of Therapeutic Targets for SARS-CoV-2 and Discovery of Potential Drugs by Computational Methods","volume":"10","author":"Wu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1080\/07391102.2021.1871958","article-title":"Enfuvirtide, an HIV-1 Fusion Inhibitor Peptide, Can Act as a Potent SARS-CoV-2 Fusion Inhibitor: An in Silico Drug Repurposing Study","volume":"40","author":"Ahmadi","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.compbiolchem.2017.11.001","article-title":"Antiviral Potential of Natural Compounds against Influenza Virus Hemagglutinin","volume":"71","author":"Kannan","year":"2017","journal-title":"Comput. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Botwina, P., Owczarek, K., Rajfur, Z., Ochman, M., Urlik, M., Nowakowska, M., Szczubia\u0142ka, K., and Pyrc, K. (2020). Berberine Hampers Influenza A Replication through Inhibition of MAPK\/ERK Pathway. Viruses, 12.","DOI":"10.3390\/v12030344"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s00705-019-04223-y","article-title":"Zeylanone Epoxide Isolated from Diospyros Anisandra Stem Bark Inhibits Influenza Virus in Vitro","volume":"164","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.antiviral.2017.03.026","article-title":"Luteolin Restricts Dengue Virus Replication through Inhibition of the Proprotein Convertase Furin","volume":"143","author":"Peng","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri3916","article-title":"New Insights into the Immunopathology and Control of Dengue Virus Infection","volume":"15","author":"Screaton","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.bmc.2014.12.015","article-title":"Flavonoids as Noncompetitive Inhibitors of Dengue Virus NS2B-NS3 Protease: Inhibition Kinetics and Docking Studies","volume":"23","author":"Wu","year":"2015","journal-title":"Bioorganic Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"25677","DOI":"10.1021\/acsomega.0c00039","article-title":"Curcumin Allosterically Inhibits the Dengue NS2B-NS3 Protease by Disrupting Its Active Conformation","volume":"5","author":"Lim","year":"2020","journal-title":"ACS Omega"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.antiviral.2018.12.002","article-title":"Inhibition of Dengue Virus by Curcuminoids","volume":"162","author":"Balasubramanian","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4103\/0972-9062.184848","article-title":"In Silico Evaluation of Inhibitory Potential of Triterpenoids from Azadirachta Indica against Therapeutic Target of Dengue Virus, NS2B-NS3 Protease","volume":"53","author":"Dwivedi","year":"2016","journal-title":"J. Vector Borne Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Bharadwaj, S., Lee, K.E., Dwivedi, V.D., Yadava, U., Panwar, A., Lucas, S.J., Pandey, A., and Kang, S.G. (2019). Discovery of Ganoderma Lucidum Triterpenoids as Potential Inhibitors against Dengue Virus NS2B-NS3 Protease. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55723-5"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"113287","DOI":"10.1016\/j.ejmech.2021.113287","article-title":"Design, Synthesis, and Structure Activity Relationship Analysis of New Betulinic Acid Derivatives as Potent HIV Inhibitors","volume":"215","author":"Zhao","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"115298","DOI":"10.1016\/j.molliq.2021.115298","article-title":"A Computational Approach for the Screening of Potential Antiviral Compounds against SARS-CoV-2 Protease: Ionic Liquid vs Herbal and Natural Compounds","volume":"326","author":"Saraswat","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/1084822317713300","article-title":"The Role of Vitamins and Minerals on the Immune System","volume":"29","author":"Alpert","year":"2017","journal-title":"Home Health Care Manag. Pract."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liang, Y., Chen, B., Liang, D., Quan, X., Gu, R., Meng, Z., Gan, H., Wu, Z., Sun, Y., and Liu, S. (2023). Pharmacological Effects of Astragaloside IV: A Review. Molecules, 28.","DOI":"10.3390\/molecules28166118"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e1309","DOI":"10.1002\/iid3.1309","article-title":"Astragaloside IV Inhibits Inflammation Caused by Influenza Virus via Reactive Oxygen Species\/NOD-like Receptor Thermal Protein Domain Associated Protein 3\/Caspase-1 Signaling Pathway","volume":"12","author":"Huang","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1002\/ddr.21995","article-title":"Berberine Ameliorates Pulmonary Inflammation in Mice with Influenza Viral Pneumonia by Inhibiting NLRP3 Inflammasome Activation and Gasdermin D-mediated Pyroptosis","volume":"83","author":"An","year":"2022","journal-title":"Drug Dev. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e10386","DOI":"10.1016\/j.heliyon.2022.e10386","article-title":"The Therapeutic Potential of Houttuynia Cordata: A Current Review","volume":"8","author":"Laldinsangi","year":"2022","journal-title":"Heliyon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1007\/s12272-015-0585-8","article-title":"Flavonoids from the Aerial Parts of Houttuynia Cordata Attenuate Lung Inflammation in Mice","volume":"38","author":"Lee","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"107618","DOI":"10.1016\/j.pharmthera.2020.107618","article-title":"Glycyrrhizin: An Alternative Drug for the Treatment of COVID-19 Infection and the Associated Respiratory Syndrome?","volume":"214","author":"Bailly","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.2174\/1389557521666210210160237","article-title":"Glycyrrhizin as a Potential Treatment for the Novel Coronavirus (COVID-19)","volume":"21","author":"Grundmann","year":"2021","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/ptr.6852","article-title":"Glycyrrhizin: An Old Weapon against a Novel Coronavirus","volume":"35","author":"Chrzanowski","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e05990","DOI":"10.1016\/j.heliyon.2021.e05990","article-title":"Can Echinacea Be a Potential Candidate to Target Immunity, Inflammation, and Infection\u2014The Trinity of Coronavirus Disease 2019","volume":"7","author":"Javed","year":"2021","journal-title":"Heliyon"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Xu, J., Xu, Z., and Zheng, W. (2017). A Review of the Antiviral Role of Green Tea Catechins. Molecules, 22.","DOI":"10.3390\/molecules22081337"},{"key":"ref_83","first-page":"1147","article-title":"Interfering With Lipid Raft Association: A Mechanism to Control Influenza Virus Infection By Sambucus Nigra","volume":"16","author":"Shahsavandi","year":"2017","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jff.2019.01.031","article-title":"Anti-Influenza Activity of Elderberry (Sambucus Nigra)","volume":"54","author":"Torabian","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2515690X20978394","DOI":"10.1177\/2515690X20978394","article-title":"Review of Whole Plant Extracts With Activity Against Herpes Simplex Viruses In Vitro and In Vivo","volume":"26","author":"Garber","year":"2021","journal-title":"J. Evid. Based Integr. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Uwamahoro, H., Collier, W.E., Nashar, T.O., Jaynes, J.M., Mortley, D.G., Davis, C.G., Kanyairita, G.G., Abdelazim, E.F., Igiramaboko, J.F.R., and Habineza, C. (2025). Natural and Designed Cyclic Peptides as Potential Antiviral Drugs to Combat Future Coronavirus Outbreaks. Molecules, 30.","DOI":"10.3390\/molecules30081651"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1007\/s43440-022-00432-6","article-title":"Antiviral Peptides against SARS-CoV-2: Therapeutic Targets, Mechanistic Antiviral Activity, and Efficient Delivery","volume":"74","author":"Essa","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Alvizo-B\u00e1ez, C.A., de Jes\u00fas Gonz\u00e1lez-Escobedo, M., Terrazas-Armend\u00e1riz, L.D., Uscanga-Palomeque, A.C., Luna-Cruz, I.E., Mart\u00ednez-Ru\u00edz, A.M., Ru\u00edz-Robles, M.A., P\u00e9rez-Tijerina, E.G., Tamez-Guerra, R., and Rodr\u00edguez-Padilla, C. (2025). Quercetin Self-Assembly Nanoparticles with Antiviral Molecules Are Effective in Inhibiting SARS-CoV-2 Pseudovirus Infection. Front. Nanotechnol., 7.","DOI":"10.3389\/fnano.2025.1579997"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106355","DOI":"10.1016\/j.jff.2024.106355","article-title":"Nanotechnology and Flavonoids: Current Research and Future Perspectives on Cardiovascular Health","volume":"120","author":"Dalimunthe","year":"2024","journal-title":"J. Funct. Foods"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"125135","DOI":"10.1016\/j.ijpharm.2024.125135","article-title":"Nanoparticle-Based Flavonoid Therapeutics: Pioneering Biomedical Applications in Antioxidants, Cancer Treatment, Cardiovascular Health, Neuroprotection, and Cosmeceuticals","volume":"670","author":"Morsy","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"221","DOI":"10.5455\/jabet.2024.d19","article-title":"Antiviral Potential of Terpenoids against Major Viral Infections: Recent Advances, Challenges, and Opportunities","volume":"7","author":"Orosco","year":"2024","journal-title":"J. Adv. Biotechnol. Exp. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"\u017digrayov\u00e1, D., Miku\u0161ov\u00e1, V., and Miku\u0161, P. (2023). Advances in Antiviral Delivery Systems and Chitosan-Based Polymeric and Nanoparticulate Antivirals and Antiviral Carriers. Viruses, 15.","DOI":"10.3390\/v15030647"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, G., and Ling, J. (2022). Medicinal Fungi with Antiviral Effect. Molecules, 27.","DOI":"10.3390\/molecules27144457"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ndeboko, B., Hantz, O., Lemamy, G.J., and Cova, L. (2018). Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway. Biomolecules, 8.","DOI":"10.3390\/biom8030055"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ymthe.2020.11.030","article-title":"Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms","volume":"29","author":"Dad","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Negreanu-Pirjol, B.S., Negreanu-Pirjol, T., Popoviciu, D.R., Anton, R.E., and Prelipcean, A.M. (2022). Marine Bioactive Compounds Derived from Macroalgae as New Potential Players in Drug Delivery Systems: A Review. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091781"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1021\/acsabm.0c00707","article-title":"Self-Assembled Peptide Drug Delivery Systems","volume":"4","author":"Yang","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.2147\/IJN.S454794","article-title":"Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine","volume":"19","author":"Yang","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.dental.2020.12.004","article-title":"Fighting Viruses with Materials Science: Prospects for Antivirus Surfaces, Drug Delivery Systems and Artificial Intelligence","volume":"37","author":"Rosa","year":"2021","journal-title":"Dent. Mater."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1021\/acs.chemmater.2c03003","article-title":"The Future of Drug Delivery","volume":"35","author":"Gao","year":"2023","journal-title":"Chem. Mater."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Satchanska, G., Davidova, S., and Petrov, P.D. (2024). Natural and Synthetic Polymers for Biomedical and Environmental Applications. Polymers, 16.","DOI":"10.3390\/polym16081159"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"117627","DOI":"10.1016\/j.lfs.2020.117627","article-title":"Virtual Screening and Repurposing of FDA Approved Drugs against COVID-19 Main Protease","volume":"251","author":"Kandeel","year":"2020","journal-title":"Life Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"W199","DOI":"10.1093\/nar\/gks450","article-title":"AVPpred: Collection and Prediction of Highly Effective Antiviral Peptides","volume":"40","author":"Thakur","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1002\/mef2.32","article-title":"VDDB: A Comprehensive Resource and Machine Learning Tool for Antiviral Drug Discovery","volume":"2","author":"Tao","year":"2023","journal-title":"MedComm\u2013Future Med."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhu, Y., Sun, X., Ma, T., Lao, X., and Zheng, H. (2023). DRAVP: A Comprehensive Database of Antiviral Peptides and Proteins. Viruses, 15.","DOI":"10.3390\/v15040820"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:55:07Z","timestamp":1760633707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/10\/1467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":105,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["biom15101467"],"URL":"https:\/\/doi.org\/10.3390\/biom15101467","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}