{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:56:45Z","timestamp":1780624605386,"version":"3.54.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1081954"],"award-info":[{"award-number":["1081954"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1105760"],"award-info":[{"award-number":["1105760"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Department of Education and Training | Australian Research Council","doi-asserted-by":"publisher","award":["DP170104431"],"award-info":[{"award-number":["DP170104431"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Recently we reported on the efficacy of pentosan polysulfate (PPS), a heparan sulfate mimetic, to reduce the recruitment of inflammatory infiltrates and protect the cartilage matrix from degradation in Ross River virus (RRV)-infected PPS-treated mice. Here, we describe both prophylactic and therapeutic treatment with PG545, a low-molecular-weight heparan sulfate mimetic, for arthritogenic alphaviral infection. We first assessed antiviral activity\n            <jats:italic>in vitro<\/jats:italic>\n            through a 50% plaque reduction assay. Increasing concentrations of PG545 inhibited plaque formation prior to viral adsorption in viral strains RRV T48, Barmah Forest virus 2193, East\/Central\/South African chikungunya virus (CHIKV), and Asian CHIKV, suggesting a strong antiviral mode of action. The viral particle-compound dissociation constant was then evaluated through isothermal titration calorimetry. Furthermore, prophylactic RRV-infected PG545-treated mice had reduced viral titers in target organs corresponding to lower clinical scores of limb weakness and immune infiltrate recruitment. At peak disease, PG545-treated RRV-infected mice had lower concentrations of the matrix-degrading enzyme heparanase in conjunction with a protective effect on tissue morphology, as seen in the histopathology of skeletal muscle. Enzyme-linked immunosorbent assay quantification of cartilage oligomeric matrix protein and cross-linked C-telopeptides of type II collagen as well as knee histopathology showed increased matrix protein degradation and cartilage erosion in RRV-infected phosphate-buffered saline-treated mice compared to their PG545-treated RRV-infected counterparts. Taken together, these findings suggest that PG545 has a direct antiviral effect on arthritogenic alphaviral infection and curtails RRV-induced inflammatory disease when administered as a prophylaxis.\n          <\/jats:p>","DOI":"10.1128\/aac.01959-17","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T09:44:43Z","timestamp":1517910283000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Prophylactic Antiheparanase Activity by PG545 Is Antiviral\n            <i>In Vitro<\/i>\n            and Protects against Ross River Virus Disease in Mice"],"prefix":"10.1128","volume":"62","author":[{"given":"Aroon","family":"Supramaniam","sequence":"first","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Ferro","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, the University of Queensland, Brisbane, QLD, Australia"},{"name":"Australian Infectious Diseases Research Centre, the University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-9828","authenticated-orcid":false,"given":"Lara J.","family":"Herrero","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000130537.76808.26"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.909-932.2001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005070"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ento.47.091201.145100"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1326-6756.2004.00436.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1179\/2047773214Y.0000000163"},{"key":"e_1_3_3_8_2","first-page":"168","article-title":"Cytology of synovial effusions in epidemic polyarthritis","volume":"11","author":"Fraser J","year":"1981","unstructured":"Fraser J, Cunningham A, Clarris B, Aaskov J, Leach R. 1981. 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