{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:19:18Z","timestamp":1790299158409,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Beneficienza Intesa Sanpaolo","award":["grant 2020-2021"],"award-info":[{"award-number":["grant 2020-2021"]}]},{"name":"Istituto Buddista Italiano Soka Gakkai","award":["grant 2021"],"award-info":[{"award-number":["grant 2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.<\/jats:p>","DOI":"10.3390\/v13091745","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:55:22Z","timestamp":1630972522000},"page":"1745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2258-0531","authenticated-orcid":false,"given":"Luisa","family":"Diomede","sequence":"first","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-3846","authenticated-orcid":false,"given":"Sara","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"De Luigi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Piotti","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-8786","authenticated-orcid":false,"given":"Jacopo","family":"Lucchetti","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Fracasso","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3690-1877","authenticated-orcid":false,"given":"Luca","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-4063","authenticated-orcid":false,"given":"Valerio","family":"Bonaldo","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38122 Trento, Italy"},{"name":"Dulbecco Telethon Institute, University of Trento, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Panini","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Filippini","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fiordaliso","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Corbelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-6704","authenticated-orcid":false,"given":"Marten","family":"Beeg","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-1483","authenticated-orcid":false,"given":"Massimo","family":"Pizzato","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-6225","authenticated-orcid":false,"given":"Marco","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Biasini","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38122 Trento, Italy"},{"name":"Dulbecco Telethon Institute, University of Trento, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Salmona","sequence":"additional","affiliation":[{"name":"Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, 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