{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:41:31Z","timestamp":1792024891961,"version":"4.4.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side effect. One alternative, with structural similarities to heparin, is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated, and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using nuclear magnetic resonance spectroscopy and liquid chromatography\u2013mass spectrometry, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective in inhibiting cell infection than low-molecular-weight heparin (on a weight\/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1055\/a-1807-0168","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T20:01:11Z","timestamp":1648065671000},"page":"984-997","source":"Crossref","is-referenced-by-count":25,"title":["Pentosan Polysulfate Inhibits Attachment and Infection by SARS-CoV-2 In Vitro: Insights into Structural Requirements for Binding"],"prefix":"10.1055","volume":"122","author":[{"given":"Sabrina","family":"Bertini","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Alekseeva","sequence":"additional","affiliation":[{"name":"Centro Alta Tecnologia \u201cIstituto di Ricerche Chimiche e Biochimiche G. Ronzoni\u201d Srl, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Elli","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Pagani","sequence":"additional","affiliation":[{"name":"Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Zanzoni","sequence":"additional","affiliation":[{"name":"Centro Piattaforme Tecnologiche, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Eisele","sequence":"additional","affiliation":[{"name":"Centro Alta Tecnologia \u201cIstituto di Ricerche Chimiche e Biochimiche G. Ronzoni\u201d Srl, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Paradigm Biopharmaceuticals Ltd., Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus P.","family":"Maag","sequence":"additional","affiliation":[{"name":"Bene PharmaChem GmbH & Co.KG, Geretsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Reiter","sequence":"additional","affiliation":[{"name":"Paradigm Biopharmaceuticals Ltd., Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Lenhart","sequence":"additional","affiliation":[{"name":"Bene PharmaChem GmbH & Co.KG, Geretsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Gruber","sequence":"additional","affiliation":[{"name":"Bene PharmaChem GmbH & Co.KG, Geretsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin A","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vicenzi","sequence":"additional","affiliation":[{"name":"Viral Pathogenesis and Biosafety Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Naggi","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche G. 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