{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:19:16Z","timestamp":1790299156014,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research, Development and Innovation Office of Hungary","award":["K119509"],"award-info":[{"award-number":["K119509"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index.<\/jats:p>","DOI":"10.3390\/ph13070139","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T11:17:17Z","timestamp":1593429437000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity"],"prefix":"10.3390","volume":"13","author":[{"given":"Zsolt","family":"Sz\u0171cs","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, H-4032 Debrecen, Hungary"},{"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen, Egyetem t\u00e9r 1, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-9302","authenticated-orcid":false,"given":"Lieve","family":"Naesens","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Stevaert","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Ostorh\u00e1zi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-1828","authenticated-orcid":false,"given":"Gyula","family":"Batta","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1l","family":"Herczegh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-4547","authenticated-orcid":false,"given":"Anik\u00f3","family":"Borb\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/irv.12504","article-title":"Risk factors for serious outcomes associated with influenza illness in high- versus low- and middle-income countries: Systematic literature review and meta-analysis","volume":"12","author":"Coleman","year":"2018","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/femsre\/fuv039","article-title":"Influenza A virus transmission via respiratory aerosols or droplets as it relates to pandemic potential","volume":"40","author":"Richard","year":"2016","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nrd2400","article-title":"The war against influenza: Discovery and development of sialidase inhibitors","volume":"6","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.antiviral.2018.10.008","article-title":"In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit","volume":"160","author":"Noshi","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.antiviral.2009.02.198","article-title":"T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections","volume":"82","author":"Furuta","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dong, G., Peng, C., Luo, J., Wang, C., Han, L., Wu, B., Ji, G., and He, H. (2015). Adamantane-resistant influenza A viruses in the world (1902\u20132013): Frequency and distribution of M2 gene mutations. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119115"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.antiviral.2013.03.014","article-title":"Influenza virus resistance to neuraminidase inhibitors","volume":"98","author":"Samson","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1056\/NEJMp0900648","article-title":"Global transmission of oseltamivir-resistant influenza","volume":"360","author":"Moscona","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/irv.12047","article-title":"Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance","volume":"7","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/med.21289","article-title":"Emerging antiviral strategies to interfere with influenza virus entry","volume":"34","author":"Vanderlinden","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.coph.2016.08.003","article-title":"Antiviral therapies on the horizon for influenza","volume":"30","author":"Naesens","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.3389\/fimmu.2018.01547","article-title":"Advancements in host-based interventions for influenza treatment","volume":"9","author":"Yip","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ijantimicag.2016.07.004","article-title":"Fighting viruses with antibiotics: An overlooked path","volume":"48","author":"Colson","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3389\/fimmu.2019.00531","article-title":"Drug repurposing approaches for the treatment of influenza viral infection: Reviving old drugs to fight against a long-lived enemy","volume":"10","author":"Pizzorno","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2015.11.003","article-title":"Teicoplanin inhibits Ebola pseudovirus infection in cell culture","volume":"125","author":"Wang","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9218","DOI":"10.1074\/jbc.M116.716100","article-title":"Glycopeptide antibiotics potently inhibit cathepsin L in the late endosome\/lysosome and block the entry of Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus (SARS-CoV)","volume":"291","author":"Zhou","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1021\/jm0300882","article-title":"Antiretroviral activity of semisynthetic derivatives of glycopeptide antibiotics","volume":"46","author":"Balzarini","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.antiviral.2006.04.008","article-title":"Polycyclic peptide and glycopeptide antibiotics and their derivatives as inhibitors of HIV entry","volume":"71","author":"Preobrazhenskaya","year":"2006","journal-title":"Antivir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.antiviral.2006.03.005","article-title":"Inhibition of feline (FIPV) and human (SARS) coronavirus by semisynthetic derivatives of glycopeptide antibiotics","volume":"72","author":"Balzarini","year":"2006","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/jac\/dkr104","article-title":"Inhibition of hepatitis C virus replication by semi-synthetic derivatives of glycopeptide antibiotics","volume":"66","author":"Obeid","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"De Burghgraeve, T., Kaptein, S.J., Ayala-Nunez, N.V., Mondotte, J.A., Pastorino, B., Printsevskaya, S.S., de Lamballerie, X., Jacobs, M., Preobrazhenskaya, M., and Gamarnik, A.V. (2012). An analogue of the antibiotic teicoplanin prevents Flavivirus entry in vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037244"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.antiviral.2009.01.003","article-title":"Anti-influenza virus activity and structure\u2013activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains","volume":"82","author":"Naesens","year":"2009","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9416","DOI":"10.1128\/JVI.07032-11","article-title":"Intracytoplasmic trapping of influenza virus by a lipophilic derivative of aglycoristocetin","volume":"86","author":"Vanderlinden","year":"2012","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1021\/jm900950d","article-title":"Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: An aggregation and receptor binding study","volume":"52","author":"Batta","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ejmech.2012.10.030","article-title":"Synthesis of fluorescent ristocetin aglycone derivatives with remarkable antibacterial and antiviral activities","volume":"58","author":"Sipos","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1016\/j.bmcl.2012.09.079","article-title":"Synthesis of isoindole and benzoisoindole derivatives of teicoplanin pseudoaglycone with remarkable antibacterial and antiviral activities","volume":"22","author":"Sipos","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejmech.2015.02.028","article-title":"A few atoms make the difference: Synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycone derivatives","volume":"94","author":"Bereczki","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1016\/j.bmcl.2014.06.018","article-title":"Semisynthetic teicoplanin derivatives as new influenza virus binding inhibitors: Synthesis and antiviral studies","volume":"24","author":"Bereczki","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/ja.2016.80","article-title":"Synthesis and biological evaluation of lipophilic teicoplanin pseudoaglycone derivatives containing a substituted triazole function","volume":"70","author":"Batta","year":"2017","journal-title":"J. Antibiot."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.ejmech.2018.08.058","article-title":"Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents","volume":"157","author":"Kelemen","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1021\/jm0500774","article-title":"Structure-activity relationship studies of a series of antiviral and antibacterial aglycon derivatives of the glycopeptide antibiotics vancomycin, eremomycin, and dechloroeremomycin","volume":"48","author":"Printsevskaya","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1021\/jo941809v","article-title":"Structural modifications of the active site in teicoplanin and related glycopeptides. 1. Reductive hydrolysis of the 1,2- and 2,3-peptide bonds","volume":"61","author":"Malabarba","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.7164\/antibiotics.40.49","article-title":"Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VIII. Opening of the polypeptide chain of teicoplanin aglycone under hydrolytic conditions","volume":"40","author":"Cavalleri","year":"1987","journal-title":"J. Antibiot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1021\/jo9506746","article-title":"Structural modifications of the active site in teicoplanin and related glycopeptides. 2. Deglucoteicoplanin-derived tetrapeptide","volume":"61","author":"Malabarba","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1039\/c39870001694","article-title":"The Edman degradation of vancomycin - Preparation of vancomycin hexapeptide","volume":"1987","author":"Booth","year":"1987","journal-title":"J. Chem. Soc Chem Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1021\/jm801549b","article-title":"Synthesis and evaluation of vancomycin aglycon analogues that bear modifications in the N-terminal d-leucyl amino acid","volume":"52","author":"Crane","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1002\/asia.201100432","article-title":"Click chemistry: 1,2,3-triazoles as pharmacophores","volume":"6","author":"Agalave","year":"2011","journal-title":"Chem. Asian J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"115130","DOI":"10.1016\/j.bmc.2019.115130","article-title":"Superior inhibition of influenza virus hemagglutinin-mediated fusion by indole-substituted spirothiazolidinones","volume":"28","author":"Zopun","year":"2020","journal-title":"Bioorg. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1099\/jgv.0.001235","article-title":"Influenza virus entry via the GM3 ganglioside-mediated platelet-derived growth factor receptor beta signalling pathway","volume":"100","author":"Vrijens","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10524","DOI":"10.1128\/JVI.00832-13","article-title":"Mutational analysis of the binding pockets of the diketo acid inhibitor L-742,001 in the influenza virus PA endonuclease","volume":"87","author":"Stevaert","year":"2013","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1800330","DOI":"10.1002\/ardp.201800330","article-title":"Synthesis and anti-coronavirus activity of a series of 1-thia-4-azaspiro [4.5]decan-3-one derivatives","volume":"352","author":"Apaydin","year":"2019","journal-title":"Arch. Pharm."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/7\/139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:44:43Z","timestamp":1760175883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/7\/139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ph13070139"],"URL":"https:\/\/doi.org\/10.3390\/ph13070139","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]}}}