{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:07:07Z","timestamp":1785229627369,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-016776"],"award-info":[{"award-number":["INV-016776"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method\/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics16101262","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T11:19:33Z","timestamp":1727435973000},"page":"1262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multidrug Combinations against SARS-CoV-2 Using GS-441524 or Ivermectin with Molnupiravir and\/or Nirmatrelvir in Reconstituted Human Nasal Airway Epithelia"],"prefix":"10.3390","volume":"16","author":[{"given":"Denise","family":"Siegrist","sequence":"first","affiliation":[{"name":"Spiez Laboratory, Federal Office for Civil Protection, 3700 Spiez, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-5970","authenticated-orcid":false,"given":"Hulda R.","family":"Jonsdottir","sequence":"additional","affiliation":[{"name":"Spiez Laboratory, Federal Office for Civil Protection, 3700 Spiez, Switzerland"},{"name":"Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland"},{"name":"Department of Rheumatology and Immunology, Inselspital University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mendy","family":"Bouveret","sequence":"additional","affiliation":[{"name":"Epithelix S\u00e0rl, Plan-les-Ouates, 1228 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Boda","sequence":"additional","affiliation":[{"name":"Epithelix S\u00e0rl, Plan-les-Ouates, 1228 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Constant","sequence":"additional","affiliation":[{"name":"Epithelix S\u00e0rl, Plan-les-Ouates, 1228 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8404-1496","authenticated-orcid":false,"given":"Olivier B.","family":"Engler","sequence":"additional","affiliation":[{"name":"Spiez Laboratory, Federal Office for Civil Protection, 3700 Spiez, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","article-title":"A SARS-CoV-2 protein interaction map reveals targets for drug repurposing","volume":"583","author":"Gordon","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2023184","article-title":"Repurposed Antiviral Drugs for Covid-19\u2014Interim WHO Solidarity Trial Results","volume":"384","author":"Pan","year":"2021","journal-title":"N. 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