{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:16:23Z","timestamp":1791486983510,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1102792"],"award-info":[{"award-number":["1102792"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Influenza viruses cause significant morbidity and mortality, especially in young children, elderly, pregnant women and individuals with co\u2010morbidities. Patients with severe influenza disease are typically treated with one neuraminidase inhibitor, oseltamivir or zanamivir. These antivirals need to be taken early to be most effective and often lead to the emergence of drug resistance and\/or decreased drug susceptibility. Combining oseltamivir with another antiviral with an alternative mode of action has the potential to improve clinical effectiveness and reduce drug resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we utilized a host\u2010targeting molecule RM\u20105061, a second\u2010generation thiazolide, in combination with oseltamivir to determine whether these compounds could reduce viral burden and understand their effects on the immune response to influenza virus infection in mice, compared with either monotherapy or placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combination of RM\u20105061 and OST administered for 5\u00a0days after influenza infection reduced viral burden at day 5 post\u2010infection, when compared to placebo and RM\u20105061 monotherapy, but was not significantly different from oseltamivir monotherapy. The inflammatory cytokine milieu was also reduced in animals which received a combination therapy when compared to RM\u20105061 and placebo\u2010treated animals. Antiviral treatment in all groups led to a reduction in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell responses in the BAL when compared to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To our knowledge, this is the first time a combination of a host\u2010targeting compound, RM\u20105061, and neuraminidase inhibitor, OST, has been tested in vivo. This antiviral combination was safe in mice and led to reduced inflammatory responses following viral infection when compared to untreated animals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/irv.12776","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T01:35:01Z","timestamp":1593135301000},"page":"678-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Viral burden, inflammatory milieu and CD8\n                    <sup>+<\/sup>\n                    T\u2010cell responses to influenza virus in a second\u2010generation thiazolide (RM\u20105061) and oseltamivir combination therapy study"],"prefix":"10.1111","volume":"14","author":[{"given":"Simone","family":"N\u00fcssing","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edin","family":"Mifsud","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"},{"name":"Victorian Infectious Diseases Reference Laboratory (VIDRL) Peter Doherty Institute for Infection and Immunity WHO Collaborating Centre for Reference and Research on Influenza Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Hensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Koutsakos","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Kedzierski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Francois","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Romark Laboratories L.C. Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-4314","authenticated-orcid":false,"given":"Aeron C.","family":"Hurt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"},{"name":"Victorian Infectious Diseases Reference Laboratory (VIDRL) Peter Doherty Institute for Infection and Immunity WHO Collaborating Centre for Reference and Research on Influenza Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-335X","authenticated-orcid":false,"given":"Katherine","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0002-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb04038.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050740"},{"key":"e_1_2_9_6_1","unstructured":"UeharaT Shionogi and Co.L S\u2010033188 a small molecule inhibitor of cap\u2010dependent endonuclease of influenza A and B Virus leads to rapid and profound viral load reduction. 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