Influence of Sex and 1,25α Dihydroxyvitamin D3 on SARS-CoV-2 Infection and Viral Entry

DOI record: { "DOI": "10.3390/pathogens14080765", "ISSN": [ "2076-0817" ], "URL": "http://dx.doi.org/10.3390/pathogens14080765", "abstract": "<jats:p>Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the etiologic agent that causes the coronavirus disease (COVID-19) identified in Wuhan, in 2019. Men are more prone to developing severe manifestations than women, suggesting a possible crucial role of sex hormones. 17,β-Estradiol (E2) and 1,25 α dihydroxyvitamin D3 (calcitriol) act upon gene pathways as immunomodulators in several infectious respiratory diseases. In this study, we aimed to evaluate the influence of E2 and calcitriol on the VSV-based pseudovirus SARS-CoV-2 and SARS-CoV-2 infection in vitro. We infected Vero E6 cells with the recombinant VSV-based pseudovirus SARS-CoV-2 and the SARS-CoV-2 viruses according to the pre-treatment and pre–post-treatment models. The Angiotensin-Converting Enzyme 2 (ACE2) and Vitamin D Receptor (VDR) gene expression did not change under different treatments. The VSV-based pseudovirus SARS-CoV-2 infection showed a significant decrease in the focus-forming unit count in the presence of E2 and calcitriol (either alone or in combination) in the pre-treatment model, while in the pre–post-treatment model, the infection was inhibited only in the presence of E2. Th SARS-CoV-2 infection highlighted a decrease in viral titres in the presence of E2 and calcitriol only in the pre–post-treatment model. 17,β-Estradiol and calcitriol can exert an inhibitory effect on SARS-CoV-2 infections, demonstrating their protective role against viral infections.</jats:p>", "alternative-id": [ "pathogens14080765" ], "author": [ { "ORCID": "https://orcid.org/0009-0005-7453-2151", "affiliation": [ { "name": "Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy" } ], "authenticated-orcid": false, "family": "Vercellino", "given": "Nicole", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0003-2397-7079", "affiliation": [ { "name": "Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy" }, { "name": "National PhD Programme in One Health Approaches to Infectious Diseases and Life Science Research, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy" } ], "authenticated-orcid": false, "family": "Ferrari", "given": "Alessandro", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-3707-3118", "affiliation": [ { "name": "Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Università degli Studi di Pavia, 27100 Pavia, Italy" } ], "authenticated-orcid": false, "family": "Sammartino", "given": "José Camilla", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-1488-8736", "affiliation": [ { "name": "Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy" }, { "name": "Center for Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, 28100 Novara, Italy" }, { "name": "Department of Internal Medicine and Rheumatology Unit, Azienda Ospedaliero-Universitaria, Maggiore della Carità, 28100 Novara, Italy" }, { "name": "Emergency Medicine Department, Azienda Ospedaliero-Universitaria, Maggiore della Carità, 28100 Novara, Italy" } ], "authenticated-orcid": false, "family": "Bellan", "given": "Mattia", "sequence": "additional" }, { "affiliation": [ { "name": "Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy" }, { "name": "National PhD Programme in One Health Approaches to Infectious Diseases and Life Science Research, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy" } ], "family": "Iskandar", "given": "Elizabeth", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-7747-7622", "affiliation": [ { "name": "Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy" } ], "authenticated-orcid": false, "family": "Lilleri", "given": "Daniele", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-7548-9731", "affiliation": [ { "name": "Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy" } ], "authenticated-orcid": false, "family": "Minisini", "given": "Rosalba", "sequence": "additional" } ], "container-title": "Pathogens", "container-title-short": "Pathogens", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 8, 6 ] ], "date-time": "2025-08-06T07:45:11Z", "timestamp": 1754466311000 }, "deposited": { "date-parts": [ [ 2025, 8, 6 ] ], "date-time": "2025-08-06T08:34:10Z", "timestamp": 1754469250000 }, "funder": [ { "DOI": "10.13039/501100003196", "award": [ "VISION 08069621" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100003196", "id-type": "DOI" } ], "name": "Ministero della Salute, Ricerca Corrente 5 × 1000 progetto" }, { "award": [ "PE00000007", "CUP F13C22001220007" ], "name": "EU funding within the NextGeneration EU-MUR -PNRR Extended Partnership initiative on Emerging Infectious Diseases INF-ACT" } ], "indexed": { "date-parts": [ [ 2025, 8, 7 ] ], "date-time": 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