{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:15:30Z","timestamp":1790727330853,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003170","name":"Stiftelsen f\u00f6r Kunskaps- och Kompetensutveckling","doi-asserted-by":"publisher","award":["20180148"],"award-info":[{"award-number":["20180148"]}],"id":[{"id":"10.13039\/501100003170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 \u03b1\u03b2, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 \u03b1\u03b2 is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 \u03b1\u03b2 against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus-1 (HIV-1). The concentration of PLNC8 \u03b1\u03b2 that is required to eliminate all the infective virus particles is in the range of nanomolar (nM) to micromolar (\u03bcM), which is surprisingly efficient considering the high content of cholesterol (8\u201335%) in their lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)\/Golgi complex, e.g. SARS-CoV-2 and flaviviruses, are considerably more susceptible to PLNC8 \u03b1\u03b2, compared to viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. Development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limit virus dissemination and spreading between individuals. PLNC8 \u03b1\u03b2 can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, more or less independent of virus antigenic mutations, which faces many antiviral drugs and vaccines.<\/jats:p>","DOI":"10.1371\/journal.pone.0278419","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T13:40:11Z","timestamp":1669815611000},"page":"e0278419","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Plantaricin NC8 \u03b1\u03b2 rapidly and efficiently inhibits flaviviruses and SARS-CoV-2 by disrupting their envelopes"],"prefix":"10.1371","volume":"17","author":[{"given":"Abubakr A. M.","family":"Omer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorma","family":"Hinkula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-9310","authenticated-orcid":true,"given":"Pham-Tue-Hung","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessam","family":"Melik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3893-7777","authenticated-orcid":true,"given":"Elisa","family":"Zattarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Aili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-1489","authenticated-orcid":true,"given":"Robert","family":"Seleg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torbj\u00f6rn","family":"Bengtsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3373-7864","authenticated-orcid":true,"given":"Hazem","family":"Khalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"pone.0278419.ref001","first-page":"176","article-title":"Antiviral Agents","author":"E Paintsil","year":"2019","journal-title":"Encyclopedia of Microbiology"},{"issue":"3","key":"pone.0278419.ref002","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the Past 50","volume":"29","author":"E De Clercq","year":"2016","journal-title":"Years. Clin Microbiol Rev"},{"issue":"3","key":"pone.0278419.ref003","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/d41573-020-00016-0","article-title":"Therapeutic options for the 2019 novel coronavirus (2019-nCoV)","volume":"19","author":"G Li","year":"2020","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"pone.0278419.ref004","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cell.2018.02.054","article-title":"Common Features of Enveloped Viruses and Implications for Immunogen Design for Next-Generation Vaccines","volume":"172","author":"FA Rey","year":"2018","journal-title":"Cell"},{"issue":"1","key":"pone.0278419.ref005","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1038\/s41467-020-17986-9","article-title":"A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2","volume":"11","author":"H Zhao","year":"2020","journal-title":"Nat Commun"},{"issue":"7","key":"pone.0278419.ref006","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1073\/pnas.0909587107","article-title":"A broad-spectrum antiviral targeting entry of enveloped viruses","volume":"107","author":"MC Wolf","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pone.0278419.ref007","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.2217\/fvl.15.53","article-title":"Addressing viral resistance through vaccines","volume":"10","author":"C Laughlin","year":"2015","journal-title":"Future Virol"},{"issue":"7871","key":"pone.0278419.ref008","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization","volume":"596","author":"D Planas","year":"2021","journal-title":"Nature"},{"issue":"4","key":"pone.0278419.ref009","doi-asserted-by":"crossref","first-page":"e0250780","DOI":"10.1371\/journal.pone.0250780","article-title":"Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein","volume":"16","author":"D Van Egeren","year":"2021","journal-title":"PLoS One"},{"issue":"4","key":"pone.0278419.ref010","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1021\/acsptsci.0c00059","article-title":"The Potential of Antimicrobial Peptides as an Antiviral Therapy against COVID-19","volume":"3","author":"S Elnagdy","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"1","key":"pone.0278419.ref011","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1128\/AEM.69.1.383-389.2003","article-title":"Purification and genetic characterization of plantaricin NC8, a novel coculture-inducible two-peptide bacteriocin from Lactobacillus plantarum NC8","volume":"69","author":"A Maldonado","year":"2003","journal-title":"Applied and environmental microbiology"},{"issue":"1","key":"pone.0278419.ref012","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s00203-003-0606-8","article-title":"Production of plantaricin NC8 by Lactobacillus plantarum NC8 is induced in the presence of different types of gram-positive bacteria","volume":"181","author":"A Maldonado","year":"2004","journal-title":"Archives of microbiology"},{"key":"pone.0278419.ref013","first-page":"45","article-title":"Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations","author":"S Soltani","year":"2021","journal-title":"FEMS Microbiol Rev"},{"issue":"1","key":"pone.0278419.ref014","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40779-021-00343-2","article-title":"Antimicrobial peptides: mechanism of action, activity and clinical potential","volume":"8","author":"Q-Y Zhang","year":"2021","journal-title":"Military Medical Research"},{"key":"pone.0278419.ref015","doi-asserted-by":"crossref","first-page":"675391","DOI":"10.1155\/2013\/675391","article-title":"Antimicrobial peptides: versatile biological properties","volume":"2013","author":"M Pushpanathan","year":"2013","journal-title":"Int J Pept"},{"issue":"1","key":"pone.0278419.ref016","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1038\/s41598-020-60570-w","article-title":"Plantaricin NC8 alphabeta exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics","volume":"10","author":"T Bengtsson","year":"2020","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0278419.ref017","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1128\/MMBR.62.4.1171-1190.1998","article-title":"Virus maturation by budding","volume":"62","author":"H Garoff","year":"1998","journal-title":"Microbiol Mol Biol Rev"},{"issue":"2","key":"pone.0278419.ref018","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: where they are and how they behave","volume":"9","author":"G van Meer","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"pone.0278419.ref019","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20092167","article-title":"Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues","volume":"20","author":"D Casares","year":"2019","journal-title":"International journal of molecular sciences"},{"key":"pone.0278419.ref020","first-page":"75","article-title":"Dual action of bacteriocin PLNC8 alphabeta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation","author":"T Bengtsson","year":"2017","journal-title":"Pathogens and disease"},{"issue":"4648","key":"pone.0278419.ref021","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1126\/science.6200935","article-title":"Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (Htlv-Iii) from Patients with Aids and Pre-Aids","volume":"224","author":"M Popovic","year":"1984","journal-title":"Science"},{"issue":"3","key":"pone.0278419.ref022","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/aid.1989.5.253","article-title":"Origin of the Hiv-Susceptible Human Cd4 + Cell-Line H9","volume":"5","author":"DL Mann","year":"1989","journal-title":"Aids Res Hum Retrov"},{"issue":"1","key":"pone.0278419.ref023","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0022-2836(65)80093-6","article-title":"Diffusion of univalent ions across the lamellae of swollen phospholipids","volume":"13","author":"AD Bangham","year":"1965","journal-title":"J Mol Biol"},{"issue":"5","key":"pone.0278419.ref024","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00802-20","article-title":"Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding","volume":"5","author":"JR Byrnes","year":"2020","journal-title":"mSphere"},{"issue":"11","key":"pone.0278419.ref025","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2020.25.11.2000266","article-title":"Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020","volume":"25","author":"A Haveri","year":"2020","journal-title":"Euro Surveill"},{"issue":"6505","key":"pone.0278419.ref026","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.abc6284","article-title":"DNA vaccine protection against SARS-CoV-2 in rhesus macaques","volume":"369","author":"J Yu","year":"2020","journal-title":"Science"},{"issue":"6","key":"pone.0278419.ref027","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/irv.12408","article-title":"A comparison of hemagglutination inhibition and neutralization assays for characterizing immunity to seasonal influenza A","volume":"10","author":"S Truelove","year":"2016","journal-title":"Influenza Other Respir Viruses"},{"issue":"3","key":"pone.0278419.ref028","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jmv.1890290305","article-title":"Human immunodeficiency virus type 1 p24 production and antigenic variation in tissue culture of isolates with various growth characteristics","volume":"29","author":"VA Sundqvist","year":"1989","journal-title":"J Med Virol"},{"issue":"1\u20132","key":"pone.0278419.ref029","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0022-1759(00)00141-1","article-title":"Mapping of B-cell epitopes in rabbits immunised with various gag antigens for the production of HIV-1 gag capture ELISA reagents","volume":"238","author":"C Devito","year":"2000","journal-title":"J Immunol Methods"},{"issue":"7","key":"pone.0278419.ref030","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nature methods"},{"key":"pone.0278419.ref031","doi-asserted-by":"crossref","first-page":"20587384211002621","DOI":"10.1177\/20587384211002621","article-title":"A review: Mechanism of action of antiviral drugs","volume":"35","author":"S Kausar","year":"2021","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"6","key":"pone.0278419.ref032","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/j.1440-1746.2008.05398.x","article-title":"Ribavirin in the treatment of chronic hepatitis C","volume":"23","author":"P Martin","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"issue":"2","key":"pone.0278419.ref033","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.idc.2010.01.001","article-title":"Antiviral drug resistance: mechanisms and clinical implications","volume":"24","author":"L Strasfeld","year":"2010","journal-title":"Infect Dis Clin North Am"},{"issue":"8","key":"pone.0278419.ref034","doi-asserted-by":"crossref","DOI":"10.3390\/v11080704","article-title":"Human Antimicrobial Peptides as Therapeutics for Viral Infections","volume":"11","author":"A Ahmed","year":"2019","journal-title":"Viruses"},{"key":"pone.0278419.ref035","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.3389\/fimmu.2020.02030","article-title":"Antimicrobial Peptides as Potential Antiviral Factors in Insect Antiviral Immune Response","volume":"11","author":"M Feng","year":"2020","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0278419.ref036","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1128\/JB.186.5.1556-1564.2004","article-title":"Induction of plantaricin production in Lactobacillus plantarum NC8 after coculture with specific gram-positive bacteria is mediated by an autoinduction mechanism","volume":"186","author":"A Maldonado","year":"2004","journal-title":"Journal of bacteriology"},{"issue":"1","key":"pone.0278419.ref037","doi-asserted-by":"crossref","first-page":"12300","DOI":"10.1038\/s41598-020-69162-0","article-title":"Phosphate-dependent aggregation of [KL]n peptides affects their membranolytic activity","volume":"10","author":"E Strandberg","year":"2020","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0278419.ref038","first-page":"301","article-title":"Divalent Cations (Mg2+, Ca2+) Protect Bacterial Outer Membrane Damage by Polymyxin B","volume":"42","author":"AZ Sahalan","year":"2013","journal-title":"Sains Malays"},{"key":"pone.0278419.ref039","doi-asserted-by":"crossref","first-page":"42994","DOI":"10.1038\/srep42994","article-title":"Highly potent antimicrobial peptides from N-terminal membrane-binding region of E. coli MreB","volume":"7","author":"K Saikia","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0278419.ref040","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12866-016-0810-8","article-title":"Antibacterial effects of Lactobacillus and bacteriocin PLNC8 alphabeta on the periodontal pathogen Porphyromonas gingivalis","volume":"16","author":"H Khalaf","year":"2016","journal-title":"BMC Microbiol"},{"issue":"10","key":"pone.0278419.ref041","doi-asserted-by":"crossref","first-page":"e25333","DOI":"10.1371\/journal.pone.0025333","article-title":"Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37","volume":"6","author":"PG Barlow","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"pone.0278419.ref042","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1128\/JVI.01840-06","article-title":"Antiviral peptides targeting the west nile virus envelope protein","volume":"81","author":"F Bai","year":"2007","journal-title":"J Virol"},{"issue":"7","key":"pone.0278419.ref043","first-page":"615","article-title":"Flavivirus: From Structure to Therapeutics Development","volume":"11","author":"R Zhao","year":"2021","journal-title":"Life (Basel)"},{"key":"pone.0278419.ref044","first-page":"1","article-title":"Coronavirus genome structure and replication","volume":"287","author":"DA Brian","year":"2005","journal-title":"Curr Top Microbiol"},{"key":"pone.0278419.ref045","doi-asserted-by":"crossref","first-page":"17","DOI":"10.12703\/r\/10-17","article-title":"Membrane remodeling by SARS-CoV-2\u2014double-enveloped viral replication","volume":"10","author":"J Mohan","year":"2021","journal-title":"Fac Rev"},{"issue":"7","key":"pone.0278419.ref046","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/j.peptides.2011.05.015","article-title":"Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses","volume":"32","author":"Q Li","year":"2011","journal-title":"Peptides"},{"key":"pone.0278419.ref047","first-page":"9","article-title":"Therapeutic approaches against coronaviruses acute respiratory syndrome","author":"C Servidio","year":"2021","journal-title":"Pharmacol Res Perspect"},{"issue":"1","key":"pone.0278419.ref048","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12931-020-01479-w","article-title":"From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses","volume":"21","author":"Z Zhu","year":"2020","journal-title":"Respiratory Research"},{"issue":"1","key":"pone.0278419.ref049","doi-asserted-by":"crossref","first-page":"12514","DOI":"10.1038\/s41598-021-91682-6","article-title":"Plantaricin NC8 alphabeta prevents Staphylococcus aureus-mediated cytotoxicity and inflammatory responses of human keratinocytes","volume":"11","author":"A Musa","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0278419.ref050","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev.cellbio.19.111301.140101","article-title":"Plasma Membrane Disruption: Repair, Prevention, Adaptation","volume":"19","author":"PL McNeil","year":"2003","journal-title":"Annual Review of Cell and Developmental Biology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T13:40:57Z","timestamp":1669815657000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0278419"}},"subtitle":[],"editor":[{"given":"Luis","family":"Men\u00e9ndez-Arias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":50,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0278419","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,30]]}}}