{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:12:35Z","timestamp":1791432755822,"version":"4.3.3"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001823","name":"Ministry of Education Youth and Sports","doi-asserted-by":"publisher","award":["LTAUSA18016"],"award-info":[{"award-number":["LTAUSA18016"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministry of Education Youth and Sports","doi-asserted-by":"publisher","award":["CZ.02.1.01\/0.0\/0.0\/15 003\/0000495"],"award-info":[{"award-number":["CZ.02.1.01\/0.0\/0.0\/15 003\/0000495"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Diphyllin is a natural arylnaphtalide lignan extracted from tropical plants of particular importance in traditional Chinese medicine. This compound has been described as a potent inhibitor of vacuolar (H+)ATPases and hence of the endosomal acidification process that is required by numerous enveloped viruses to trigger their respective viral infection cascades after entering host cells by receptor-mediated endocytosis. Accordingly, we report here a revised, updated, and improved synthesis of diphyllin, and demonstrate its antiviral activities against a panel of enveloped viruses from Flaviviridae, Phenuiviridae, Rhabdoviridae, and Herpesviridae families. Diphyllin is not cytotoxic for Vero and BHK-21 cells up to 100 \u00b5M and exerts a sub-micromolar or low-micromolar antiviral activity against tick-borne encephalitis virus, West Nile virus, Zika virus, Rift Valley fever virus, rabies virus, and herpes-simplex virus type 1. Our study shows that diphyllin is a broad-spectrum host cell-targeting antiviral agent that blocks the replication of multiple phylogenetically unrelated enveloped RNA and DNA viruses. In support of this, we also demonstrate that diphyllin is more than just a vacuolar (H+)ATPase inhibitor but may employ other antiviral mechanisms of action to inhibit the replication cycles of those viruses that do not enter host cells by endocytosis followed by low pH-dependent membrane fusion.<\/jats:p>","DOI":"10.3390\/v14020354","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:26:48Z","timestamp":1644442008000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Diphyllin Shows a Broad-Spectrum Antiviral Activity against Multiple Medically Important Enveloped RNA and DNA Viruses"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-7780","authenticated-orcid":false,"given":"Michal","family":"\u0160tef\u00e1nik","sequence":"first","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zem\u011bd\u011blsk\u00e1 1665\/1, CZ-613 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dattatry Shivajirao","family":"Bhosale","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Faculty of Chemical Technology, Institute of Organic Chemistry and Technology, University of Pardubice, Studentsk\u00e1 573, CZ-532 10 Pardubice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Haviernik","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Biology Centre of the Czech Academy of Sciences, Institute of Parasitology, Brani\u0161ovsk\u00e1 1160\/31, CZ-370 05 Ceske Budejovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Strakov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Biology Centre of the Czech Academy of Sciences, Institute of Parasitology, Brani\u0161ovsk\u00e1 1160\/31, CZ-370 05 Ceske Budejovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Fojt\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Dufkov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Huvarov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Sal\u00e1t","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Biology Centre of the Czech Academy of Sciences, Institute of Parasitology, Brani\u0161ovsk\u00e1 1160\/31, CZ-370 05 Ceske Budejovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5078-7751","authenticated-orcid":false,"given":"Jan","family":"Bart\u00e1\u010dek","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Technology, Institute of Organic Chemistry and Technology, University of Pardubice, Studentsk\u00e1 573, CZ-532 10 Pardubice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-4746","authenticated-orcid":false,"given":"Jan","family":"Svoboda","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Technology, Institute of Organic Chemistry and Technology, University of Pardubice, Studentsk\u00e1 573, CZ-532 10 Pardubice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-812X","authenticated-orcid":false,"given":"Milo\u0161","family":"Sedl\u00e1k","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Technology, Institute of Organic Chemistry and Technology, University of Pardubice, Studentsk\u00e1 573, CZ-532 10 Pardubice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-2380","authenticated-orcid":false,"given":"Daniel","family":"R\u016f\u017eek","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Biology Centre of the Czech Academy of Sciences, Institute of Parasitology, Brani\u0161ovsk\u00e1 1160\/31, CZ-370 05 Ceske Budejovice, Czech Republic"},{"name":"Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 735\/5, CZ-625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-249X","authenticated-orcid":false,"given":"Andrew D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zem\u011bd\u011blsk\u00e1 1665\/1, CZ-613 00 Brno, Czech Republic"},{"name":"KP Therapeutics (Europe) s.r.o., Purky\u0148ova 649\/127, CZ-612 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lud\u011bk","family":"Eyer","sequence":"additional","affiliation":[{"name":"Laboratory of Emerging Viral Diseases, Veterinary Research Institute, Hudcova 296\/70, CZ-621 00 Brno, Czech Republic"},{"name":"Biology Centre of the Czech Academy of Sciences, Institute of Parasitology, Brani\u0161ovsk\u00e1 1160\/31, CZ-370 05 Ceske Budejovice, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/pca.2565","article-title":"Arylnaphthalene and aryltetralin-type lignans in hairy root cultures ofLinum perenne, and the stereochemistry of 6-methoxypodophyllotoxin and one diastereoisomer by HPLC-MS and NMR spectroscopy","volume":"26","author":"Lesur","year":"2015","journal-title":"Phytochem. Anal."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cui, Q., Du, R., Liu, M., and Rong, L. (2020). Lignans and Their Derivatives from Plants as Antivirals. Molecules, 25.","DOI":"10.3390\/molecules25010183"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1080\/14786419.2020.1758090","article-title":"New cyclopeptide alkaloids from the whole plant of Justicia procumbens L.","volume":"35","author":"Lv","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1248\/cpb.51.1299","article-title":"Arylnaphthalide Lignans from Cleistanthus collinus","volume":"51","author":"Ramesh","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1515\/znc-1996-9-1002","article-title":"Topical Anti-Inflammatory Lignans from Haplophyllum hispanicum Haplophyllum hispanicum","volume":"51","author":"Prieto","year":"1996","journal-title":"Zeitschrift Naturforschung C"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1359\/jbmr.070613","article-title":"Diphyllin, a Novel and Naturally Potent V-ATPase Inhibitor, Abrogates Acidification of the Osteoclastic Resorption Lacunae and Bone Resorption","volume":"22","author":"Henriksen","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ejphar.2011.05.042","article-title":"Effects of diphyllin as a novel V-ATPase inhibitor on gastric adenocarcinoma","volume":"667","author":"Shen","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ejphar.2015.12.026","article-title":"ZT-25, a new vacuolar H -ATPase inhibitor, induces apoptosis and protective autophagy through ROS generation in HepG2 cells","volume":"771","author":"Lu","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ejmech.2014.06.002","article-title":"Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H -ATPase inhibitors","volume":"82","author":"Zhang","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-93506-5_1","article-title":"The Search for Anticancer Agents from Tropical Plants","volume":"107","author":"Henkin","year":"2018","journal-title":"Prog. Chem. Org. Nat. Prod. Prog. Chem. Org. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/ardp.201200035","article-title":"Synthesis and Bioevaluation of Diphyllin Glycosides as Novel Anticancer Agents","volume":"345","author":"Zhao","year":"2012","journal-title":"Arch. Pharma."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jep.2005.07.021","article-title":"Anti-inflammatory activities of constituents isolated from Phyllanthus polyphyllus","volume":"103","author":"Rao","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ebiom.2019.08.060","article-title":"Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus","volume":"47","author":"Persaud","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.abb.2008.03.025","article-title":"Function, structure and regulation of the vacuolar (H+)-ATPases","volume":"476","author":"Jefferies","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hu, Y.-B., Dammer, E.B., Ren, R.-J., and Wang, G. (2015). The endosomal-lysosomal system: From acidification and cargo sorting to neurodegeneration. Transl. Neurodegener., 4.","DOI":"10.1186\/s40035-015-0041-1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/tra.12389","article-title":"Fusion of Enveloped Viruses in Endosomes","volume":"17","author":"White","year":"2016","journal-title":"Traffic"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hu, C.-M.J., Chang, W.-S., Fang, Z.-S., Chen, Y.-T., Wang, W.-L., Tsai, H.-H., Chueh, L.-L., Takano, T., Hohdatsu, T., and Chen, H.-W. (2017). Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13316-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1055\/s-2006-962087","article-title":"The Antiviral Action of Lignans","volume":"55","author":"MacRae","year":"1989","journal-title":"Planta Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rocha, M., Campana, P., Scoaris, D., Almeida, V., Lopes, J., Shaw, J., and Silva, C. (2018). Combined In Vitro Studies and in Silico Target Fishing for the Evaluation of the Biological Activities of Diphylleia cymosa and Podophyllum hexandrum. Molecules, 23.","DOI":"10.3390\/molecules23123303"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thamburaj, S., Ramaraj, E., Sethupathy, S., Kamalanathan, C., Raji, A., and Rajasekharan, S.K. (2020). Antibacterial and antibiofilm activities of diphyllin against fish pathogens. Microb. Pathog., 145.","DOI":"10.1016\/j.micpath.2020.104232"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1055\/s-2005-864106","article-title":"In Vitro Antileishmanial Activity of Diphyllin Isolated fromHaplophyllum bucharicum","volume":"71","author":"Giorgio","year":"2005","journal-title":"Planta Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.antiviral.2013.06.014","article-title":"Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses","volume":"99","author":"Chen","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.phytochem.2017.01.005","article-title":"Anti-HIV diphyllin glycosides from Justicia gendarussa","volume":"136","author":"Zhang","year":"2017","journal-title":"Phytochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1021\/acs.jnatprod.7b00004","article-title":"Potent Inhibitor of Drug-Resistant HIV-1 Strains Identified from the Medicinal Plant Justicia gendarussa","volume":"80","author":"Zhang","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0031-9422(96)00024-6","article-title":"Antiviral activity of lignans and their glycosides from Justicia procumbens","volume":"42","author":"Asano","year":"1996","journal-title":"Phytochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Stefanik, M., Strakova, P., Haviernik, J., Miller, A.D., Ruzek, D., and Eyer, L. (2021). Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030471"},{"key":"ref_27","unstructured":"Kozuch, O., and Mayer, P. (1975). Pig Kidney Epithelial (Ps) Cells\u2014Perfect Tool for Study of Flavi-Viruses and Some Other Arboviruses. Acta Virol., 19."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1099\/vir.0.010058-0","article-title":"Morphological changes in human neural cells following tick-borne encephalitis virus infection","volume":"90","author":"Ahantarig","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_29","first-page":"113","article-title":"A simple micro-culture method for the study of group B arboviruses","volume":"40","author":"Porterfield","year":"1969","journal-title":"Bull. World Health Organ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74425","DOI":"10.1039\/C5RA13746B","article-title":"Synthesis, biological evaluation and molecular modeling of 1H-benzo[d]imidazole derivatives as novel anti-tubulin polymerization agents","volume":"5","author":"Wang","year":"2015","journal-title":"RSC Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0960-894X(01)80523-0","article-title":"Synthesis of ring-a-opened isopicropodophyllins as potential DNA topoisomerase II inhibitors","volume":"4","author":"Kamal","year":"1994","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_32","first-page":"921","article-title":"Effects of diphyllin as a novel V-ATPase inhibitor on TE-1 and ECA-109 cells","volume":"39","author":"Chen","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"95999","DOI":"10.18632\/oncotarget.21625","article-title":"Differential modulation Of BAX\/BCL-2 ratio and onset of caspase-3\/7 Activation induced by derivatives of JUSTICIDIN B in human melanoma CELLS A375","volume":"8","author":"Gibbons","year":"2017","journal-title":"Oncotarget"},{"key":"ref_34","first-page":"6217","article-title":"Cleistanthin A inhibits the invasion and metastasis of human melanoma cells by inhibiting the expression of matrix metallopeptidase-2 and -9","volume":"14","author":"Pan","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s43440-019-00012-1","article-title":"Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: Involvement of the \u03b2-catenin pathway","volume":"72","author":"Liu","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1021\/np060430o","article-title":"Lignans from Dysosma versipellis with Inhibitory Effects on Prostate Cancer Cell Lines","volume":"70","author":"Jiang","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ctrv.2009.08.003","article-title":"V-ATPase inhibitors and implication in cancer treatment","volume":"35","author":"Rey","year":"2009","journal-title":"Cancer Treat Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/s10637-010-9425-3","article-title":"D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase II\u03b1","volume":"29","author":"Gui","year":"2010","journal-title":"Investig. New Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.phymed.2010.04.001","article-title":"Arylnaphthalene lignans from Taiwania cryptomerioides as novel blockers of voltage-gated K channels","volume":"18","author":"Leung","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yi, L., Chen, L., Guo, X., Lu, T., Wang, H., Ji, X., Zhang, J., Ren, Y., Pan, P., and Douglas Kinghorn, A.D. (2018). A Synthetic Disaccharide Derivative of Diphyllin, TAARD, Activates Human Natural Killer Cells to Secrete Interferon-Gamma via Toll-Like Receptor-Mediated NF-\u03baB and STAT3 Signaling Pathways. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01509"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1021\/np0101651","article-title":"Potent Cytotoxic Lignans from Justicia procumbens and Their Effects on Nitric Oxide and Tumor Necrosis Factor-\u03b1 Production in Mouse Macrophages","volume":"65","author":"Day","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1476-5381.2011.01346.x","article-title":"The proton translocation domain of cellular vacuolar ATPase provides a target for the treatment of influenza A virus infections","volume":"164","author":"Kainov","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00705-013-1797-1","article-title":"Entry of human rhinovirus 89 via ICAM-1 into HeLa epithelial cells is inhibited by actin skeleton disruption and by bafilomycin","volume":"159","author":"Pfanzagl","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dabydeen, S.A., and Meneses, P.I. (2009). The role of NH4Cl and cysteine proteases in Human Papillomavirus type 16 infection. Virol. J., 20.","DOI":"10.1186\/1743-422X-6-109"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Watanabe, S.M., Ehrlich, L.S., Strickland, M., Li, X., Soloveva, V., Goff, A.J., Stauft, C.B., Bhaduri-McIntosh, S., Tjandra, N., and Carter, C. (2020). Selective Targeting of Virus Replication by Proton Pump Inhibitors. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-60544-y"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/2\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:09Z","timestamp":1760134629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/2\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["v14020354"],"URL":"https:\/\/doi.org\/10.3390\/v14020354","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]}}}