Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell culture and primary human nasal epithelial cells by blocking viral entry

{ 'indexed': {'date-parts': [[2023, 5, 9]], 'date-time': '2023-05-09T17:30:50Z', 'timestamp': 1683653450960}, 'reference-count': 46, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2022, 12, 6]], 'date-time': '2022-12-06T00:00:00Z', 'timestamp': 1670284800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2022, 12, 6]], 'date-time': '2022-12-06T00:00:00Z', 'timestamp': 1670284800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100003323', 'name': 'Agence Nationale de Recherches sur le Sida et les Hépatites Virales', 'doi-asserted-by': 'crossref'}, { 'DOI': '10.13039/501100002915', 'name': 'Fondation pour la Recherche Médicale', 'doi-asserted-by': 'crossref', 'award': ['ANR Flash COVID']}, { 'DOI': '10.13039/501100001665', 'name': 'Agence Nationale de la Recherche', 'doi-asserted-by': 'crossref', 'award': ['ANR Flash COVID']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>The 2019 global coronavirus (COVID-19) pandemic has ' 'brought the world to a grinding halt, highlighting the urgent need for therapeutic and ' 'preventive solutions to slow the spread of emerging viruses. The objective of this study was ' 'to assess the anti-SARS-CoV-2 effectiveness of 8 FDA-approved cationic amphiphilic drugs ' '(CADs). SARS-CoV-2-infected Vero cells, Calu-3 cells and primary Human Nasal Epithelial Cells ' '(HNEC) were used to investigate the effects of CADs and revealed their antiviral mode of ' 'action. Among the CADs tested, desloratadine, a commonly used antiallergic, well-tolerated ' 'with no major side effects, potently reduced the production of SARS-CoV-2 RNA in Vero-E6 ' 'cells. Interestingly, desloratadine was also effective against HCoV-229E and HCoV-OC43 ' 'showing that it possessed broad-spectrum anti-coronavirus activity. Investigation of its mode ' 'of action revealed that it targeted an early step of virus lifecycle and blocked SARS-CoV-2 ' 'entry through the endosomal pathway. Finally, the ex vivo kinetic of the antiviral effect of ' 'desloratadine was evaluated on primary Human Nasal Epithelial Cells (HNEC), showing a ' 'significant delay of viral RNA production with a maximal reduction reached after 72\xa0h of ' 'treatment. Thus, this treatment could provide a substantial contribution to prophylaxis and ' 'systemic therapy of COVID-19 or other coronaviruses infections and requires further ' 'studies.</jats:p>', 'DOI': '10.1038/s41598-022-25399-5', 'type': 'journal-article', 'created': {'date-parts': [[2022, 12, 6]], 'date-time': '2022-12-06T12:46:12Z', 'timestamp': 1670330772000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 1, 'title': 'Desloratadine, an FDA-approved cationic amphiphilic drug, inhibits SARS-CoV-2 infection in cell ' 'culture and primary human nasal epithelial cells by blocking viral entry', 'prefix': '10.1038', 'volume': '12', 'author': [ {'given': 'Margot', 'family': 'Morin-Dewaele', 'sequence': 'first', 'affiliation': []}, {'given': 'Sophie', 'family': 'Bartier', 'sequence': 'additional', 'affiliation': []}, {'given': 'François', 'family': 'Berry', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rozenn', 'family': 'Brillet', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Dennis Salomón', 'family': 'López-Molina', 'sequence': 'additional', 'affiliation': []}, {'given': 'Công Trung', 'family': 'Nguyễn', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pascale', 'family': 'Maille', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kevin', 'family': 'Sereno', 'sequence': 'additional', 'affiliation': []}, {'given': 'Quentin', 'family': 'Nevers', 'sequence': 'additional', 'affiliation': []}, {'given': 'Laurent', 'family': 'Softic', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jean-Marie', 'family': 'Vaugeois', 'sequence': 'additional', 'affiliation': []}, {'given': 'Bruno', 'family': 'Louis', 'sequence': 'additional', 'affiliation': []}, {'given': 'Emilie', 'family': 'Bequignon', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-0719-0826', 'authenticated-orcid': False, 'given': 'Patrice', 'family': 'Bruscella', 'sequence': 'additional', 'affiliation': []}, {'given': 'André', 'family': 'Coste', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-0745-7559', 'authenticated-orcid': False, 'given': 'Jean-Michel', 'family': 'Pawlotsky', 'sequence': 'additional', 'affiliation': []}, {'given': 'Stéphane', 'family': 'Jamain', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6489-5091', 'authenticated-orcid': False, 'given': 'Abdelhakim', 'family': 'Ahmed-Belkacem', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2022, 12, 6]]}, 'reference': [ { 'issue': '20', 'key': '25399_CR1', 'doi-asserted-by': 'publisher', 'first-page': '1967', 'DOI': '10.1056/NEJMoa030747', 'volume': '348', 'author': 'C Drosten', 'year': '2003', 'unstructured': 'Drosten, C. et al. 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The rest of the ' 'authors have no competing interest.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '21053'}