{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T11:17:55Z","timestamp":1769167075119,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double-standardized blend of extracts from Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L. (EAM-ESN) or separated extracts of A. melanocarpa (EAM) or S. nigra (ESN) against four human respiratory tract viruses: influenza A virus (A\/H1N1), betacoronavirus-1 (HCoV-OC43) belonging to the same \u03b2-coronaviruses as the current pandemic SARS-CoV-2, human herpesvirus type 1 (HHV-1), and human adenovirus type 5 (HAdV-5). Antiviral assays (AVAs) were used to evaluate the antiviral activity of the plant extracts in a cell-present environment with extracts tested before, simultaneously, or after viral infection. The virus replication was assessed using the CPE scale or luminescent assay. The EAM-ESN blend strongly inhibited A\/H1N1 replication as well as HCoV-OC43, while having a limited effect against HHV-1 and HAdV-5. This activity likely depends mostly on the presence of the extract of S. nigra. However, the EAM-ESN blend possesses more effective inhibitory activity toward virus replication than its constituent extracts. A post-infection mechanism of action of the EAM-ESN make this blend the most relevant for potential drugs and supportive treatments; thus, the EAM-ESN blend might be considered as a natural remedy in mild, seasonal respiratory viral infections.<\/jats:p>","DOI":"10.3390\/ph15050619","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L."],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-1544","authenticated-orcid":false,"given":"Micha\u0142","family":"Ochnik","sequence":"first","affiliation":[{"name":"Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-0818","authenticated-orcid":false,"given":"Dominika","family":"Franz","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Sobczy\u0144ski","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Naporowski","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Microbiology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariusz","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry and Polymer Physical Chemistry, Nicolaus Copernicus University in Toru\u0144, 87-100 Toru\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Orzechowska","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-9606","authenticated-orcid":false,"given":"Marta","family":"Sochocka","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","article-title":"Influenza","volume":"390","author":"Paules","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mostafa, A., Abdelwhab, E.M., Mettenleiter, T.C., and Pleschka, S. (2018). Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview. Viruses, 10.","DOI":"10.3390\/v10090497"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","unstructured":"World Health Organization (2021, August 31). Influenza. Available online: https:\/\/www.who.int\/teams\/health-product-policy-and-standards\/standards-and-specifications\/vaccines-quality\/influenza."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the Past 50 Years","volume":"29","author":"Li","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s40265-018-0899-1","article-title":"Baloxavir: First Global Approval","volume":"78","author":"Heo","year":"2018","journal-title":"Drugs"},{"key":"ref_7","unstructured":"FDA (2021, September 04). Influenza (Flu) Antiviral Drugs and Related Information, Available online: https:\/\/www.fda.gov\/drugs\/information-drug-class\/influenza-flu-antiviral-drugs-and-related-information."},{"key":"ref_8","unstructured":"European Medicines Agency (2021, September 04). Antiviral Medicines for Pandemic Influenza. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory\/overview\/public-health-threats\/pandemic-influenza\/antiviral-medicines-pandemic-influenza."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bai, Y., Jones, J., Wong, S.-S., and Zanin, M. (2021). Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance. Viruses, 13.","DOI":"10.3390\/v13040624"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and evolution of pathogenic coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41392-020-0190-2","article-title":"Overview of lethal human coronaviruses","volume":"5","author":"Chen","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_12","unstructured":"FDA (2021, September 26). Know Your Treatment Options for COVID-19, Available online: https:\/\/www.fda.gov\/consumers\/consumer-updates\/know-your-treatment-options-covid-19."},{"key":"ref_13","unstructured":"Dimitrova, E.K., and European Medicines Agency (2021, September 26). Veklury. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/veklury."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the Treatment of COVID-19\u2014Preliminary report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fphar.2013.00177","article-title":"The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety","volume":"4","author":"Ekor","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.antiviral.2006.03.004","article-title":"Antiviral drug resistance","volume":"71","author":"Richman","year":"2006","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1016\/j.drudis.2021.05.008","article-title":"Drug combination therapy for emerging viral diseases","volume":"26","author":"Shyr","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/ptr.6575","article-title":"Antiviral activity of plants and their isolated bioactive compounds: An update","volume":"34","author":"Denaro","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/ptr.5782","article-title":"A Review of the Antiviral Properties of Black Elder (Sambucus nigra L.) Products","volume":"31","author":"Porter","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jff.2017.11.025","article-title":"Bioactive properties of Sambucus nigra L. as a functional ingredient for food and pharmaceutical industry","volume":"40","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1089\/jmf.2009.0062","article-title":"Aronia Plants: A Review of Traditional Use, Biological Activities, and Perspectives for Modern Medicine","volume":"13","author":"Kokotkiewicz","year":"2010","journal-title":"J. Med. Food"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jurikova, T., Mlcek, J., Skrovankova, S., Sumczynski, D., Sochor, J., Hlavacova, I., Snopek, L., and Orsavov\u00e1, J. (2017). Fruits of Black Chokeberry Aronia melanocarpa in the Prevention of Chronic Diseases. Molecules, 22.","DOI":"10.3390\/molecules22060944"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ptr.2729","article-title":"A systematic review on the sambuci fructus effect and efficacy profiles. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives","volume":"24","author":"Vlachojannis","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zheng, J., Chen, F., Wu, K., Wang, J., Li, F., Huang, S., Lu, J., Huang, J., Liu, H., and Zhou, R. (2021). Clinical and virological impact of single and dual infections with influenza A (H1N1) and SARS-CoV-2 in adult inpatients. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009997"},{"key":"ref_25","first-page":"209","article-title":"Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses","volume":"45","author":"Knox","year":"2001","journal-title":"Acta Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1021\/np50090a003","article-title":"Synergistic Effect of Flavones and Flavonols against Herpes Simplex Virus Type 1 in Cell Culture. Comparison with the Antiviral Activity of Propolis","volume":"55","author":"Amoros","year":"1992","journal-title":"J. Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Musarra-Pizzo, M., Pennisi, R., Ben-Amor, I., Smeriglio, A., Mandalari, G., and Sciortino, M.T. (2020). In Vitro Anti-HSV-1 Activity of Polyphenol-Rich Extracts and Pure Polyphenol Compounds Derived from Pistachios Kernels (Pistacia vera L.). Plants, 9.","DOI":"10.3390\/plants9020267"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.tim.2021.03.014","article-title":"Respiratory mucus as a virus-host range determinant","volume":"29","author":"Wallace","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6563","DOI":"10.1007\/s00216-013-7068-x","article-title":"Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry","volume":"405","author":"Swaminathan","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1080\/07391102.2017.1413422","article-title":"The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus","volume":"36","author":"Kannan","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"786","DOI":"10.5352\/JLS.2015.25.7.786","article-title":"Antioxidative Effect and Neuraminidase Inhibitory Activity of Polyphenols Isolated from a New Korean Red Waxy Sorghum (Sorghum bicolor L. cv. Hwanggeumchalsusu)","volume":"25","author":"Ra","year":"2015","journal-title":"J. Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chojnacka, K., Skrzypczak, D., Izydorczyk, G., Mikula, K., Szopa, D., and Witek-Krowiak, A. (2021). Antiviral Properties of Polyphenols from Plants. Foods, 10.","DOI":"10.3390\/foods10102277"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.3389\/fphar.2019.01207","article-title":"The Signaling Pathways, and Therapeutic Targets of Antiviral Agents: Focusing on the Antiviral Approaches and Clinical Perspectives of Anthocyanins in the Management of Viral Diseases","volume":"10","author":"Pour","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"590509","DOI":"10.3389\/fphar.2021.590509","article-title":"Anti\u2013SARS-CoV-2 Natural Products as Potentially Therapeutic Agents","volume":"12","author":"Kim","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_35","first-page":"905215","article-title":"Bioavailability of Dietary Polyphenols and Gut Microbiota Metabolism: Antimicrobial Properties","volume":"2015","author":"Villar","year":"2015","journal-title":"BioMed. Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1021\/jf100315d","article-title":"Bioavailability of Anthocyanins and Ellagitannins Following Consumption of Raspberries by Healthy Humans and Subjects with an Ileostomy","volume":"58","author":"Borges","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/ajcn\/73.5.920","article-title":"Anthocyanins are absorbed in glycated forms in elderly women: A pharmacokinetic study","volume":"73","author":"Cao","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1093\/jn\/132.7.1865","article-title":"Absorption and Metabolism of Anthocyanins in Elderly Women after Consumption of Elderberry or Blueberry","volume":"132","author":"Wu","year":"2002","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"230S","DOI":"10.1093\/ajcn\/81.1.230S","article-title":"Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies","volume":"81","author":"Manach","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.phytochem.2009.06.003","article-title":"Elderberry flavonoids bind to and prevent H1N1 infection in vitro","volume":"70","author":"Roschek","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1080\/14786419.2017.1299724","article-title":"Comparison of different methods for extraction of Cinnamomi ramulus: Yield, chemical composition and in vitro antiviral activities","volume":"31","author":"Zhou","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Krawitz, C., Abu Mraheil, M., Stein, M., Imirzalioglu, C., Domann, E., Pleschka, S., and Hain, T. (2011). Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement. Altern. Med., 11.","DOI":"10.1186\/1472-6882-11-16"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1271\/bbb.120112","article-title":"Anti-Influenza Virus Effects of Elderberry Juice and Its Fractions","volume":"76","author":"Kinoshita","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2013.08.090","article-title":"Aronia melanocarpa and its components demonstrate antiviral activity against influenza viruses","volume":"440","author":"Park","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"85","DOI":"10.5501\/wjv.v5.i2.85","article-title":"Determination of 50% endpoint titer using a simple formula","volume":"5","author":"Ramakrishnan","year":"2016","journal-title":"World J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"da Silva, R.F.R., Barreira, J.C.M., Heleno, S.A., Barros, L., Calhelha, R.C., and Ferreira, I.C.F.R. (2019). Anthocyanin Profile of Elderberry Juice: A Natural-Based Bioactive Colouring Ingredient with Potential Food Application. Molecules, 24.","DOI":"10.3390\/molecules24132359"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1002\/jsfa.3029","article-title":"Anthocyanins and other polyphenolics in American elderberry (Sambucus canadensis) and European elderberry (S. nigra) cultivars","volume":"87","author":"Lee","year":"2007","journal-title":"J. Sci. Food Agric."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska, A., Siudem, P., Paradowska, K., Gralec, M., Ka\u017amierski, S., and Wawer, I. (2020). Aronia melanocarpa Fruits as a Rich Dietary Source of Chlorogenic Acids and Anthocyanins: 1H-NMR, HPLC-DAD, and Chemometric Studies. Molecules, 25.","DOI":"10.3390\/molecules25143234"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7846","DOI":"10.1021\/jf0486850","article-title":"Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia, and Sambucus and their antioxidant capacity","volume":"52","author":"Wu","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","first-page":"e751","article-title":"Titration of Human Coronaviruses Using an Immunoperoxidase Assay","volume":"14","author":"Lambert","year":"2008","journal-title":"JoVE J. Vis. Exp."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.3389\/fmicb.2019.02367","article-title":"Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of Ginkgo biloba (EGb) and Its Phytochemical Constituents","volume":"10","author":"Sochocka","year":"2019","journal-title":"Front. Microbiol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:13:37Z","timestamp":1760138017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/5\/619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ph15050619"],"URL":"https:\/\/doi.org\/10.3390\/ph15050619","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]}}}