{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:52Z","timestamp":1787030032484,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDATION ARC","award":["JA 20161204585"],"award-info":[{"award-number":["JA 20161204585"]}]},{"name":"FONDATION ARC","award":["ANRS0379"],"award-info":[{"award-number":["ANRS0379"]}]},{"name":"Agence Nnationale de recherches sur le sida et les h\u00e9patites virales (ANRS)","award":["JA 20161204585"],"award-info":[{"award-number":["JA 20161204585"]}]},{"name":"Agence Nnationale de recherches sur le sida et les h\u00e9patites virales (ANRS)","award":["ANRS0379"],"award-info":[{"award-number":["ANRS0379"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Heparan sulfate proteoglycans (HSPGs) are a major constituent of the extracellular matrix (ECM) and are found to be implicated in viral infections, where they play a role in both cell entry and release for many viruses. The enzyme heparanase-1 is the only known endo-beta-D-glucuronidase capable of degrading heparan sulphate (HS) chains of HSPGs and is thus important for regulating ECM homeostasis. Heparanase-1 expression is tightly regulated as the uncontrolled cleavage of HS may result in abnormal cell activation and significant tissue damage. The overexpression of heparanase-1 correlates with pathological scenarios and is observed in different human malignancies, such as lymphoma, breast, colon, lung, and hepatocellular carcinomas. Interestingly, heparanase-1 has also been documented to be involved in numerous viral infections, e.g., HSV-1, HPV, DENV. Moreover, very recent reports have demonstrated a role of heparanase-1 in HCV and SARS-CoV-2 infections. Due to the undenied pro-carcinogenic role of heparanase-1, multiple inhibitors have been developed, some reaching phase II and III in clinical studies. However, the use of heparanase inhibitors as antivirals has not yet been proposed. If it can be assumed that heparanase-1 is implicated in numerous viral life cycles, its inhibition by specific heparanase-acting compounds should result in a blockage of viral infection. This review addresses the perspectives of using heparanase inhibitors, not only for cancer treatment, but also as antivirals. Eventually, the development of a novel class antivirals targeting a cellular protein could help to alleviate the resistance problems seen with some current antiretroviral therapies.<\/jats:p>","DOI":"10.3390\/v15010237","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:10:34Z","timestamp":1673838634000},"page":"237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Heparanase-1: From Cancer Biology to a Future Antiviral Target"],"prefix":"10.3390","volume":"15","author":[{"given":"Nadjet","family":"Lebsir","sequence":"first","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Centre de Recherche en Canc\u00e9rologie de Lyon, 69434 Lyon, France"},{"name":"Confluence: Sciences et Humanit\u00e9s (EA 1598), UCLy, 10 Place des Archives, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-0083","authenticated-orcid":false,"given":"Fabien","family":"Zoulim","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Centre de Recherche en Canc\u00e9rologie de Lyon, 69434 Lyon, France"},{"name":"Hospices Civils de Lyon, 69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-7779","authenticated-orcid":false,"given":"Boyan","family":"Grigorov","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre L\u00e9on B\u00e9rard, Centre de Recherche en Canc\u00e9rologie de Lyon, 69434 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.drup.2016.10.001","article-title":"Heparanase: From Basic Research to Therapeutic Applications in Cancer and Inflammation","volume":"29","author":"Vlodavsky","year":"2016","journal-title":"Drug Resist. 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