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In this project, HS\u2013virus interactions were targeted by a new fucosylated chondroitin sulfate from the sea cucumber Pentacta pygmaea (PpFucCS) in order to block human cytomegalovirus (HCMV) entry into cells. Human foreskin fibroblasts were infected with HCMV in the presence of PpFucCS and its low molecular weight (LMW) fractions and the virus yield at five days post-infection was assessed. The virus attachment and entry into the cells were visualized by labeling the purified virus particles with a self-quenching fluorophore octadecyl rhodamine B (R18). The native PpFucCS exhibited potent inhibitory activity against HCMV specifically blocking virus entry into the cell and the inhibitory activities of the LMW PpFucCS derivatives were proportional to their chain lengths. PpFucCS and the derived oligosaccharides did not exhibit any significant cytotoxicity; moreover, they protected the infected cells from virus-induced lytic cell death. In conclusion, PpFucCS inhibits the entry of HCMV into cells and the high MW of this carbohydrate is a key structural element to achieve the maximal anti-viral effect. This new marine sulfated glycan can be developed into a potential prophylactic and therapeutic antiviral agent against HCMV infection.<\/jats:p>","DOI":"10.3390\/v15040859","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T02:58:21Z","timestamp":1679972301000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of Cytomegalovirus by Pentacta pygmaea Fucosylated Chondroitin Sulfate Depends on Its Molecular Weight"],"prefix":"10.3390","volume":"15","author":[{"given":"Poonam","family":"Sharma","sequence":"first","affiliation":[{"name":"Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Mississippi, Oxford, MS 38655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Ray","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanti","family":"Shukla","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-8880","authenticated-orcid":false,"given":"Vitor H.","family":"Pomin","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Mississippi, Oxford, MS 38655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-8840","authenticated-orcid":false,"given":"Ritesh","family":"Tandon","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Research, Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"},{"name":"Department of Biomolecular Sciences, University of Mississippi, Oxford, MS 38655, USA"},{"name":"Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","unstructured":"Wilkins, L.W. (2006). Fields Virology, Wolters Kluwer Health. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/590934","article-title":"Immunocompromised hosts: Perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients","volume":"47","author":"Boucher","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e02392-16","DOI":"10.1128\/JVI.02392-16","article-title":"Congenital Human Cytomegalovirus Infection and the Enigma of Maternal Immunity","volume":"91","author":"Britt","year":"2017","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41579-021-00582-z","article-title":"Pathogenesis of human cytomegalovirus in the immunocompromised host","volume":"19","author":"Griffiths","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2165\/00023210-200216050-00003","article-title":"CNS manifestations of cytomegalovirus infections: Diagnosis and treatment","volume":"16","author":"Maschke","year":"2002","journal-title":"CNS Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mitra, D., Hasan, M.H., Bates, J.T., Bidwell, G.L., and Tandon, R. (2021). Tegument Protein pp150 Sequence-Specific Peptide Blocks Cytomegalovirus Infection. Viruses, 13.","DOI":"10.3390\/v13112277"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.1093\/infdis\/jiz389","article-title":"The Development of Therapeutics for the Treatment and Prevention of CMV Disease in the Transplant Population: A Regulatory Perspective","volume":"221","author":"Hodowanec","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_8","first-page":"27","article-title":"A Treatment Advance for Patients with Posttransplant CMV","volume":"327","author":"Voelker","year":"2022","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1128\/CMR.00009-10","article-title":"Antiviral drug resistance of human cytomegalovirus","volume":"23","author":"Lurain","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/QCO.0000000000000170","article-title":"Approach to drug-resistant cytomegalovirus in transplant recipients","volume":"28","author":"Chou","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1182\/blood-2016-06-688432","article-title":"How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients","volume":"128","author":"Shah","year":"2016","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e01987-20","DOI":"10.1128\/JVI.01987-20","article-title":"Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives","volume":"95","author":"Tandon","year":"2021","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a004952","DOI":"10.1101\/cshperspect.a004952","article-title":"Heparan sulfate proteoglycans","volume":"3","author":"Sarrazin","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1172\/JCI200113799","article-title":"Herpesviruses and heparan sulfate: An intimate relationship in aid of viral entry","volume":"108","author":"Shukla","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mitra, D., Hasan, M.H., Bates, J.T., Bierdeman, M.A., Ederer, D.R., Parmar, R.C., Fassero, L.A., Liang, Q., Qiu, H., and Tiwari, V. (2021). The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009803"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1038\/s41467-019-10587-1","article-title":"CD46 facilitates entry and dissemination of human cytomegalovirus","volume":"10","author":"Stein","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gerna, G., Kabanova, A., and Lilleri, D. (2019). Human Cytomegalovirus Cell Tropism and Host Cell Receptors. Vaccines, 7.","DOI":"10.3390\/vaccines7030070"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1099\/jgv.0.001230","article-title":"Cytomegalovirus host entry and spread","volume":"100","author":"Farrell","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.coviro.2012.01.001","article-title":"Human cytomegalovirus entry into cells","volume":"2","author":"Vanarsdall","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1006\/viro.1993.1192","article-title":"Initiation of human cytomegalovirus infection requires initial interaction with cell surface heparan sulfate","volume":"193","author":"Compton","year":"1993","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4751","DOI":"10.1128\/AAC.00854-13","article-title":"A peptide inhibitor of cytomegalovirus infection from human hemofiltrate","volume":"57","author":"Borst","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1128\/JVI.00109-15","article-title":"A role for 3-O-sulfated heparan sulfate in promoting human cytomegalovirus infection in human iris cells","volume":"89","author":"Baldwin","year":"2015","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nguyen, C.C., and Kamil, J.P. (2018). Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism. Viruses, 10.","DOI":"10.20944\/preprints201811.0378.v2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00781-18","DOI":"10.1128\/mBio.00781-18","article-title":"CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells","volume":"9","author":"Vanarsdall","year":"2018","journal-title":"mBio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e01206-16","DOI":"10.1128\/JVI.01206-16","article-title":"Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling to Enter and Initiate the Early Steps in the Establishment of Latency in CD34+ Human Progenitor Cells","volume":"91","author":"Kim","year":"2017","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7043","DOI":"10.1073\/pnas.1814850116","article-title":"OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism","volume":"116","author":"Xiaofei","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cagno, V., Tseligka, E.D., Jones, S.T., and Tapparel, C. (2019). Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?. Viruses, 11.","DOI":"10.3390\/v11070596"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101207","DOI":"10.1016\/j.jbc.2021.101207","article-title":"Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection","volume":"297","author":"Dwivedi","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1161\/01.CIR.103.24.2994","article-title":"Guide to anticoagulant therapy: Heparin: A statement for healthcare professionals from the American Heart Association","volume":"103","author":"Hirsh","year":"2001","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/glycob\/cwac063","article-title":"Anti-SARS-CoV-2 and anticoagulant properties of Pentacta pygmaea fucosylated chondroitin sulfate depend on high molecular weight structures","volume":"33","author":"Dwivedi","year":"2023","journal-title":"Glycobiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101856","DOI":"10.1016\/j.jbc.2022.101856","article-title":"Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties","volume":"298","author":"Kim","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43732","DOI":"10.1021\/acsami.2c11493","article-title":"Radio Frequency Heating of Washable Conductive Textiles for Bacteria and Virus Inactivation","volume":"14","author":"Oh","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14223","DOI":"10.1073\/pnas.2334032100","article-title":"Functional profiling of a human cytomegalovirus genome","volume":"100","author":"Dunn","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1111\/jam.12654","article-title":"The influence of stabilizers and rates of freezing on preserving of structurally different animal viruses during lyophilization and subsequent storage","volume":"117","year":"2014","journal-title":"J. Appl. Microbiol."},{"key":"ref_35","unstructured":"TF Scientific (2010). Molecular Probes Handbook, Invitrogen. [11th ed.]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1747-0285.2008.00741.x","article-title":"The structure of glycosaminoglycans and their interactions with proteins","volume":"72","author":"Gandhi","year":"2008","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.2741\/4455","article-title":"Glycosaminoglycans and infection","volume":"21","author":"Aquino","year":"2016","journal-title":"Front. Biosci. Landmark Ed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105077","DOI":"10.1016\/j.antiviral.2021.105077","article-title":"Antiviral activities of four marine sulfated glycans against adenovirus and human cytomegalovirus","volume":"190","author":"Zoepfl","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117797","DOI":"10.1016\/j.carbpol.2021.117797","article-title":"Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus","volume":"260","author":"Yan","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.bbamem.2014.04.015","article-title":"Peptide entry inhibitors of enveloped viruses: The importance of interfacial hydrophobicity","volume":"1838","author":"Badani","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16004","DOI":"10.1039\/D0DT02478C","article-title":"What is holding back the development of antiviral metallodrugs? A literature overview and implications for SARS-CoV-2 therapeutics and future viral outbreaks","volume":"49","author":"Santos","year":"2020","journal-title":"Dalton Trans."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2043","DOI":"10.1002\/rmv.2043","article-title":"Marine glycan-based antiviral agents in clinical or preclinical trials","volume":"29","author":"Hao","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.ijbiomac.2020.09.184","article-title":"The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica","volume":"163","author":"Jin","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1385\/IR:25:3:193","article-title":"Neutralizing antibodies mechanism of neutralization and protective activity against HIV-1","volume":"25","author":"Xiao","year":"2002","journal-title":"Immunol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.sbi.2015.05.007","article-title":"Current structural biology of the heparin interactome","volume":"34","author":"Pomin","year":"2015","journal-title":"Curr. Opin. Struct. 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