{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:02:14Z","timestamp":1792119734487,"version":"4.4.0"},"reference-count":91,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003524","name":"Ministry of Business, Innovation and Employment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001504","name":"Ministry of Health, New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001504","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Western Research Chair in Viral Pathogenesis"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-15428"],"award-info":[{"award-number":["FDN-15428"]}],"id":[{"id":"10.13039\/501100000024","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":[[2025,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Although myriads of potential antiviral agents have been tested against SARS-CoV-2, only a handful have proven to be effective in clinical trials. During the COVID-19 pandemic, many known or novel peptides were evaluated for their ability to inhibit SARS-CoV-2 replication; however, testing of D-enantiomers that resist body and viral proteases has been limited. Here, we characterized the ability of D-3006, a D-enantiomeric synthetic host defense peptide, to inhibit SARS-CoV-2 replication\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . A battery of authentic SARS-CoV-2 variants (ancestral, Mu, Delta, and Omicron BA.1) and a comprehensive panel of \u03b2-coronavirus spike pseudotyped lentiviruses were used to demonstrate that D-3006 safely (CC\n                      <jats:sub>50<\/jats:sub>\n                      value = 430 \u00b5g\/mL) blocked spike-mediated entry (EC\n                      <jats:sub>50<\/jats:sub>\n                      values ranging from 1.57 to 5.37 \u00b5g\/mL) and also had synergistic anti-SARS-CoV-2 activity\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      when combined with the viral polymerase inhibitor remdesivir. We also showed that D-3006 inhibited influenza A virus (H1N1) replication\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , suggesting that this synthetic host defense peptide could have potential broad antiviral activity against multiple enveloped viruses. These data, together with negative-stain transmission electron microscopy analysis, suggest that the mechanism of action of D-3006 is associated with non-specific binding to the viral membrane, most likely causing virus aggregation and interfering with virus attachment and entry. The potential broad-spectrum antiviral activity of D-3006, its innate resistance to host proteases, as well as the possibility of being used in combination with other antiviral drugs suggest that this host synthetic peptide could be developed as a candidate for the treatment of SARS-CoV-2 and\/or other respiratory viral infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01700-24","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T09:00:23Z","timestamp":1750669223000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Synthetic host defense peptide inhibits SARS-CoV-2 replication\n                    <i>in vitro<\/i>"],"prefix":"10.1128","volume":"69","author":[{"given":"Rhodri","family":"Harfoot","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair","family":"Lawley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonor C.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatric Dentistry, Schulich School of Medicine and Dentistry, Western University","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kuang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]},{"id":[{"id":"https:\/\/ror.org\/0040r6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biomedical Sciences, Victoria University of Wellington","place":["Wellington, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca R.","family":"Hills","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhra","family":"Sinha","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot J. M.","family":"Allais","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]},{"id":[{"id":"https:\/\/ror.org\/0405trq15","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Environmental Science and Research","place":["Wellington, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-0444","authenticated-orcid":true,"given":"Tom W.","family":"Bird","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0040r6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biomedical Sciences, Victoria University of Wellington","place":["Wellington, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody P.","family":"Hird","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Taylor","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03b94tp07","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, The University of Auckland","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3621-3772","authenticated-orcid":true,"given":"Mihnea","family":"Bostina","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01jmxt844","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago","place":["Dunedin, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Comoletti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0040r6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biomedical Sciences, Victoria University of Wellington","place":["Wellington, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan F.","family":"Haney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03rmrcq20","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5989-8503","authenticated-orcid":true,"given":"Robert E. 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