{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:57:50Z","timestamp":1792205870575,"version":"4.4.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018M3A9H4056340"],"award-info":[{"award-number":["2018M3A9H4056340"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Influenza viruses (IVs) have become increasingly resistant to antiviral drugs that target neuraminidase and matrix protein 2 due to gene mutations that alter their drug-binding target protein regions. Consequently, almost all recent IV pandemics have exhibited resistance to commercial antiviral vaccines. To overcome this challenge, an antiviral target is needed that is effective regardless of genetic mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>In particular, hemagglutinin (HA), a highly conserved surface protein across many IV strains, could be an effective antiviral target as it mediates binding of IVs with host cell receptors, which is crucial for membrane fusion. HA has 6 disulfide bonds that can easily bind with the surfaces of gold nanoparticles. Herein, we fabricated porous gold nanoparticles (PoGNPs) via a surfactant-free emulsion method that exhibited strong affinity for disulfide bonds due to gold\u2013thiol interactions, and provided extensive surface area for these interactions. A remarkable decrease in viral infectivity was demonstrated by increased cell viability results after exposing MDCK cells to various IV strains (H1N1, H3N2, and H9N2) treated with PoGNP. Most of all, the viability of MDCK cells infected with all IV strains increased to 96.8% after PoGNP treatment of the viruses compared to 33.9% cell viability with non-treated viruses. Intracellular viral RNA quantification by real-time RT-PCR also confirmed that PoGNP successfully inhibited viral membrane fusion by blocking the viral entry process through conformational deformation of HA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We believe that the technique described herein can be further developed for PoGNP-utilized antiviral protection as well as metal nanoparticle-based therapy to treat viral infection. Additionally, facile detection of IAV can be achieved by developing PoGNP as a multiplatform for detection of the virus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-020-00611-8","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T03:02:36Z","timestamp":1585018956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["Porous gold nanoparticles for attenuating infectivity of influenza A virus"],"prefix":"10.1186","volume":"18","author":[{"given":"Jinyoung","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjoo","family":"Yeom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeksu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Ouk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woonsung","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Woo","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geunseon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaewon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daesub","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4990-0523","authenticated-orcid":false,"given":"Seungjoo","family":"Haam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"611_CR1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1128\/CMR.00037-07","volume":"21","author":"JB Mahony","year":"2008","unstructured":"Mahony JB. Detection of respiratory viruses by molecular methods. Clin Microbiol Rev. 2008;21:716\u201347.","journal-title":"Clin Microbiol Rev"},{"key":"611_CR2","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1001\/jama.292.11.1333","volume":"292","author":"WW Thompson","year":"2004","unstructured":"Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, Fukuda K. Influenza-associated hospitalizations in the United States. JAMA. 2004;292:1333\u201340.","journal-title":"JAMA"},{"key":"611_CR3","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1086\/315320","volume":"181","author":"L Simonsen","year":"2000","unstructured":"Simonsen L, Fukuda K, Schonberger LB, Cox NJ. The impact of influenza epidemics on hospitalizations. J Infect Dis. 2000;181:831\u20137.","journal-title":"J Infect Dis"},{"key":"611_CR4","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1146\/annurev.med.51.1.407","volume":"51","author":"NJ Cox","year":"2000","unstructured":"Cox NJ, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med. 2000;51:407\u201321.","journal-title":"Annu Rev Med"},{"key":"611_CR5","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1086\/598989","volume":"48","author":"GA Poland","year":"2009","unstructured":"Poland GA, Jacobson RM, Ovsyannikova IG. Influenza virus resistance to antiviral agents: a plea for rational use. Clin Infect Dis. 2009;48:1254\u20136.","journal-title":"Clin Infect Dis"},{"key":"611_CR6","first-page":"1329","volume":"57","author":"Centers for Disease C, Prevention","year":"2008","unstructured":"Centers for Disease C, Prevention. Update: influenza activity\u2013United States. Morb Mortal Wkly Rep. 2008;57:1329\u201332.","journal-title":"Morb Mortal Wkly Rep"},{"key":"611_CR7","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1093\/jac\/dkh155","volume":"53","author":"CI Thompson","year":"2004","unstructured":"Thompson CI, Barclay WS, Zambon MC. Changes in in vitro susceptibility of influenza A H3N2 viruses to a neuraminidase inhibitor drug during evolution in the human host. J Antimicrob Chemother. 2004;53:759\u201365.","journal-title":"J Antimicrob Chemother"},{"key":"611_CR8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.antiviral.2013.03.014","volume":"98","author":"M Samson","year":"2013","unstructured":"Samson M, Pizzorno A, Abed Y, Boivin G. Influenza virus resistance to neuraminidase inhibitors. Antiviral Res. 2013;98:174\u201385.","journal-title":"Antiviral Res"},{"key":"611_CR9","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.virusres.2004.02.034","volume":"103","author":"LV Gubareva","year":"2004","unstructured":"Gubareva LV. Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors. Virus Res. 2004;103:199\u2013203.","journal-title":"Virus Res"},{"key":"611_CR10","doi-asserted-by":"publisher","first-page":"15382","DOI":"10.1073\/pnas.0807771105","volume":"105","author":"DL Floyd","year":"2008","unstructured":"Floyd DL, Ragains JR, Skehel JJ, Harrison SC, van Oijen AM. Single-particle kinetics of influenza virus membrane fusion. Proc Natl Acad Sci USA. 2008;105:15382\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"611_CR11","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/0092-8674(93)90260-W","volume":"73","author":"CM Carr","year":"1993","unstructured":"Carr CM, Kim PS. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell. 1993;73:823\u201332.","journal-title":"Cell"},{"key":"611_CR12","doi-asserted-by":"publisher","first-page":"1800960","DOI":"10.1002\/adfm.201800960","volume":"28","author":"HO Kim","year":"2018","unstructured":"Kim HO, Na W, Yeom M, Choi J, Kim J, Lim JW, Yun D, Chun H, Park G, Park C, et al. Host cell mimic polymersomes for rapid detection of highly pathogenic influenza virus via a viral fusion and cell entry mechanism. Adv Funct Mater. 2018;28:1800960.","journal-title":"Adv Funct Mater"},{"key":"611_CR13","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.abb.2015.04.011","volume":"581","author":"J Fontana","year":"2015","unstructured":"Fontana J, Steven AC. Influenza virus-mediated membrane fusion: structural insights from electron microscopy. Arch Biochem Biophys. 2015;581:86\u201397.","journal-title":"Arch Biochem Biophys"},{"key":"611_CR14","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1073\/pnas.79.4.968","volume":"79","author":"JJ Skehel","year":"1982","unstructured":"Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson IA, Wiley DC. Changes in the conformation of influenza-virus hemagglutinin at the Ph optimum of virus-mediated membrane-fusion. Proc Natl Acad Sci USA. 1982;79:968\u201372.","journal-title":"Proc Natl Acad Sci USA"},{"key":"611_CR15","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0092-8674(00)81771-7","volume":"95","author":"J Chen","year":"1998","unstructured":"Chen J, Lee KH, Steinhauer DA, Stevens DJ, Skehel JJ, Wiley DC. Structure of the hemagglutinin precursor cleavage site, a determinant of influenza pathogenicity and the origin of the labile conformation. Cell. 1998;95:409\u201317.","journal-title":"Cell"},{"key":"611_CR16","first-page":"88","volume":"17","author":"P Mehrbod","year":"2009","unstructured":"Mehrbod P, Motamed N, Tabatabaian M, Soleimani ER, Amini E, Shahidi M, Kheiri MT. In vitro antiviral effect of \u201cNanosilver\u201d on influenza virus. Daru. 2009;17:88\u201393.","journal-title":"Daru"},{"key":"611_CR17","doi-asserted-by":"publisher","first-page":"4103","DOI":"10.2147\/IJN.S53622","volume":"8","author":"D Xiang","year":"2013","unstructured":"Xiang D, Zheng Y, Duan W, Li X, Yin J, Shigdar S, O\u2019Connor ML, Marappan M, Zhao X, Miao Y, et al. Inhibition of A\/Human\/Hubei\/3\/2005 (H3N2) influenza virus infection by silver nanoparticles in vitro and in vivo. Int J Nanomed. 2013;8:4103\u201313.","journal-title":"Int J Nanomed"},{"key":"611_CR18","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1477-3155-3-6","volume":"3","author":"JL Elechiguerra","year":"2005","unstructured":"Elechiguerra JL, Burt JL, Morones JR, Camacho-Bragado A, Gao X, Lara HH, Yacaman MJ. Interaction of silver nanoparticles with HIV-1. J Nanobiotechnol. 2005;3:6.","journal-title":"J Nanobiotechnol"},{"key":"611_CR19","doi-asserted-by":"publisher","first-page":"e104113","DOI":"10.1371\/journal.pone.0104113","volume":"9","author":"P Orlowski","year":"2014","unstructured":"Orlowski P, Tomaszewska E, Gniadek M, Baska P, Nowakowska J, Sokolowska J, Nowak Z, Donten M, Celichowski G, Grobelny J, Krzyzowska M. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection. PLoS ONE. 2014;9:e104113.","journal-title":"PLoS ONE"},{"key":"611_CR20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1556-276X-8-93","volume":"8","author":"Y Mori","year":"2013","unstructured":"Mori Y, Ono T, Miyahira Y, Nguyen VQ, Matsui T, Ishihara M. Antiviral activity of silver nanoparticle\/chitosan composites against H1N1 influenza A virus. Nanoscale Res Lett. 2013;8:93.","journal-title":"Nanoscale Res Lett"},{"key":"611_CR21","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1039\/C5NR07918G","volume":"8","author":"XX Yang","year":"2016","unstructured":"Yang XX, Li CM, Huang CZ. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale. 2016;8:3040\u20138.","journal-title":"Nanoscale"},{"key":"611_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1477-3155-8-1","volume":"8","author":"HH Lara","year":"2010","unstructured":"Lara HH, Ayala-Nunez NV, Ixtepan-Turrent L, Rodriguez-Padilla C. Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnol. 2010;8:1.","journal-title":"J Nanobiotechnol"},{"key":"611_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1477-3155-8-15","volume":"8","author":"HH Lara","year":"2010","unstructured":"Lara HH, Ixtepan-Turrent L, Garza-Trevino EN, Rodriguez-Padilla C. PVP-coated silver nanoparticles block the transmission of cell-free and cell-associated HIV-1 in human cervical culture. J Nanobiotechnol. 2010;8:15.","journal-title":"J Nanobiotechnol"},{"key":"611_CR24","doi-asserted-by":"publisher","first-page":"4600","DOI":"10.1021\/nn5002485","volume":"8","author":"JH Wei","year":"2014","unstructured":"Wei JH, Zheng LT, Lv X, Bi YH, Chen WW, Zhang W, Shi Y, Zhao L, Sun XM, Wang F, et al. Analysis of influenza virus receptor specificity using glycan-functionalized gold nanoparticles. ACS Nano. 2014;8:4600\u20137.","journal-title":"ACS Nano"},{"key":"611_CR25","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1002\/smll.201001349","volume":"6","author":"I Papp","year":"2010","unstructured":"Papp I, Sieben C, Ludwig K, Roskamp M, Bottcher C, Schlecht S, Herrmann A, Haag R. Inhibition of influenza virus infection by multivalent sialic-acid-functionalized gold nanoparticles. Small. 2010;6:2900\u20136.","journal-title":"Small"},{"key":"611_CR26","doi-asserted-by":"publisher","first-page":"6896","DOI":"10.1021\/ja710321g","volume":"130","author":"MC Bowman","year":"2008","unstructured":"Bowman MC, Ballard TE, Ackerson CJ, Feldheim DL, Margolis DM, Melander C. Inhibition of HIV fusion with multivalent gold nanoparticles. J Am Chem Soc. 2008;130:6896\u20137.","journal-title":"J Am Chem Soc"},{"key":"611_CR27","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1039\/c0md00229a","volume":"2","author":"M Sametband","year":"2011","unstructured":"Sametband M, Shukla S, Meningher T, Hirsh S, Mendelson E, Sarid R, Gedanken A, Mandelboim M. Effective multi-strain inhibition of influenza virus by anionic gold nanoparticles. Medchemcomm. 2011;2:421\u20133.","journal-title":"Medchemcomm"},{"key":"611_CR28","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.msec.2018.04.005","volume":"89","author":"A Haider","year":"2018","unstructured":"Haider A, Das S, Ojha D, Chattopadhyay D, Mukherjee A. Highly monodispersed gold nanoparticles synthesis and inhibition of herpes simplex virus infections. Mater Sci Eng C-Mater Biol Appl. 2018;89:413\u201321.","journal-title":"Mater Sci Eng C-Mater Biol Appl"},{"key":"611_CR29","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/adhm.201400197","volume":"4","author":"D Bang","year":"2015","unstructured":"Bang D, Lee T, Choi J, Park Y, Kim E, Huh YM, Haam S. A multistep photothermic-driven drug release system using wire-framed Au nanobundles. Adv Healthc Mater. 2015;4:255\u201363.","journal-title":"Adv Healthc Mater"},{"key":"611_CR30","doi-asserted-by":"publisher","first-page":"13554","DOI":"10.1039\/C5RA24772A","volume":"6","author":"T Lee","year":"2016","unstructured":"Lee T, Bang D, Chang YW, Choi Y, Park KY, Oh A, Han S, Kim SH, Lee K, Suh JS, et al. Cancer theranosis using mono-disperse, mesoporous gold nanoparticles obtained via a robust, high-yield synthetic methodology. RSC Adv. 2016;6:13554\u201361.","journal-title":"RSC Adv"},{"key":"611_CR31","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1126\/science.98.2557.587","volume":"98","author":"AR Taylor","year":"1943","unstructured":"Taylor AR, Sharp DG, McLean IW Jr, Beard D, Beard JW, Dingle JH, Feller AE. Purification and character of the swine influenza virus. Science. 1943;98:587\u20139.","journal-title":"Science"},{"key":"611_CR32","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0003-2697(85)90103-4","volume":"144","author":"DJ Arora","year":"1985","unstructured":"Arora DJ, Tremblay P, Bourgault R, Boileau S. Concentration and purification of influenza virus from allantoic fluid. Anal Biochem. 1985;144:189\u201392.","journal-title":"Anal Biochem"},{"key":"611_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-28706-1","volume":"8","author":"E Kirkpatrick","year":"2018","unstructured":"Kirkpatrick E, Qiu XT, Wilson PC, Bahl J, Krammer F. The influenza virus hemagglutinin head evolves faster than the stalk domain. Sci Rep. 2018;8:1\u201314.","journal-title":"Sci Rep"},{"key":"611_CR34","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.reprotox.2015.05.011","volume":"57","author":"GL Chen","year":"2015","unstructured":"Chen GL, Zhang SB, Jin YX, Wu Y, Liu L, Qian HF, Fu ZW. TPP and TCEP induce oxidative stress and alter steroidogenesis in TM3 Leydig cells. Reprod Toxicol. 2015;57:100\u201310.","journal-title":"Reprod Toxicol"},{"key":"611_CR35","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1021\/cm500316k","volume":"26","author":"NG Bastus","year":"2014","unstructured":"Bastus NG, Merkoci F, Piella J, Puntes V. Synthesis of highly monodisperse citrate-stabilized silver nanoparticles of up to 200\u00a0nm: kinetic control and catalytic properties. Chem Mater. 2014;26:2836\u201346.","journal-title":"Chem Mater"},{"key":"611_CR36","doi-asserted-by":"publisher","first-page":"17042","DOI":"10.1021\/ja907069u","volume":"131","author":"SD Perrault","year":"2009","unstructured":"Perrault SD, Chan WC. Synthesis and surface modification of highly monodispersed, spherical gold nanoparticles of 50-200\u00a0nm. J Am Chem Soc. 2009;131:17042\u20133.","journal-title":"J Am Chem Soc"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-020-00611-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12951-020-00611-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-020-00611-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T20:19:34Z","timestamp":1616530774000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-020-00611-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["611"],"URL":"https:\/\/doi.org\/10.1186\/s12951-020-00611-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.2.20864\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.20864\/v1","asserted-by":"object"}]},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]},"assertion":[{"value":"10 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing financial interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"54"}}