{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:54:22Z","timestamp":1788432862358,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["754354"],"award-info":[{"award-number":["754354"]}]},{"name":"Werner Siemens Stiftlung","award":["754354"],"award-info":[{"award-number":["754354"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We have reported that CD-6\u2032SLN [6-sialyllactosamine (6\u2032SLN)-modified \u03b2-cyclodextrin (CD)] can be a potential anti-influenza drug because it irreversibly deactivates virions. Indeed, in vivo, CD-6\u2032SLN improved mice survival in an H1N1 infection model even when administered 24 h post-infection. Although CD-6\u2032SLN was designed to target the viral envelope protein hemagglutinin (HA), a natural receptor of 6\u2032SLN, it remains unclear whether other targets exist. In this study, we confirm that CD-6\u2032SLN inhibits the influenza virus through an extracellular mechanism by interacting with HA, but not with neuraminidase (NA), despite the latter also having a binding pocket for the sialyl group. We find that CD-6\u2032SLN interacts with the viral envelope as it elicits the release of a fluorophore embedded in the membrane. Two similar compounds were designed to test separately the effect of 6\u2032SLN and of the undecyl moiety that links the CD to 6\u2032SLN. Neither showed any interaction with the membrane nor the irreversible viral inhibition (virucidal), confirming that both components are essential to membrane interaction and virucidal action. Unlike similar antiviral cyclodextrins developed against other viruses, CD-6\u2032SLN was not able to decapsulate viral RNA. Our findings support that combining viral protein-specific epitopes with hydrophobic linkers provides a strategy for developing antiviral drugs with a virucidal mechanism.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020582","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Antiviral Mechanism of Virucidal Sialic Acid Modified Cyclodextrin"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-7864","authenticated-orcid":false,"given":"Yong","family":"Zhu","sequence":"first","affiliation":[{"name":"Institute of Materials, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, Switzerland, Station 12, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-6163","authenticated-orcid":false,"given":"Andrey A.","family":"Sysoev","sequence":"additional","affiliation":[{"name":"Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Otto-Hahn-Stra\u00dfe 11, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo H. Jacob","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute of Materials, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, Switzerland, Station 12, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Batista","sequence":"additional","affiliation":[{"name":"Institute of Materials, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, Switzerland, Station 12, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-6080","authenticated-orcid":false,"given":"Francesco","family":"Stellacci","sequence":"additional","affiliation":[{"name":"Institute of Materials, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne, Switzerland, Station 12, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: A modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"\u015awierczy\u0144ska, M., Mirowska-Guzel, D.M., and Pindelska, E. 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