{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:08:32Z","timestamp":1777363712037,"version":"3.51.4"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T00:00:00Z","timestamp":1582934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL090586"],"award-info":[{"award-number":["HL090586"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL107152"],"award-info":[{"award-number":["HL107152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) infections are wide-spread among the general population with manifestations ranging from asymptomatic to severe developmental disabilities in newborns and life-threatening illnesses in individuals with a compromised immune system. Nearly all current drugs suffer from one or more limitations, which emphasizes the critical need to develop new approaches and new molecules. We reasoned that a \u2018poly-pharmacy\u2019 approach relying on simultaneous binding to multiple receptors involved in HCMV entry into host cells could pave the way to a more effective therapeutic outcome. This work presents the study of a synthetic, small molecule displaying pleiotropicity of interactions as a competitive antagonist of viral or cell surface receptors including heparan sulfate proteoglycans and heparan sulfate-binding proteins, which play important roles in HCMV entry and spread. Sulfated pentagalloylglucoside (SPGG), a functional mimetic of heparan sulfate, inhibits HCMV entry into human foreskin fibroblasts and neuroepithelioma cells with high potency. At the same time, SPGG exhibits no toxicity at levels as high as 50-fold more than its inhibition potency. Interestingly, cell-ELISA assays showed downregulation in HCMV immediate-early gene 1 and 2 (IE 1&amp;2) expression in presence of SPGG further supporting inhibition of viral entry. Finally, HCMV foci were observed to decrease significantly in the presence of SPGG suggesting impact on viral spread too. Overall, this work offers the first evidence that pleiotropicity, such as demonstrated by SPGG, may offer a new poly-therapeutic approach toward effective inhibition of HCMV.<\/jats:p>","DOI":"10.3390\/ijms21051676","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T03:13:28Z","timestamp":1583205208000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of Human Cytomegalovirus Entry into Host Cells through A Pleiotropic Small Molecule"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-0485","authenticated-orcid":false,"given":"James","family":"Elste","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Kaltenbach","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vraj R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harsh","family":"Sharthiya","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-8840","authenticated-orcid":false,"given":"Ritesh","family":"Tandon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-3261","authenticated-orcid":false,"given":"Satish K.","family":"Mehta","sequence":"additional","affiliation":[{"name":"KBR Wyle Laboratories, Houston, TX 77058, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael V.","family":"Volin","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1852-9167","authenticated-orcid":false,"given":"Michele","family":"Fornaro","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaibhav","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies and Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-6597","authenticated-orcid":false,"given":"Umesh R.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1056\/NEJM197107222850406","article-title":"The cytomegaloviruses: Ubiquitous agents with protean clinical manifestations. 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