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In this study, we investigated the potential role of oral microbiome in SARS-CoV-2 infection. Using an\n              <jats:italic>in vitro<\/jats:italic>\n              SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by\n              <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n              on SARS-CoV-2 infection mediated by known\n              <jats:italic>P. gingivalis<\/jats:italic>\n              compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, whereas PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in\n              <jats:italic>P. gingivalis<\/jats:italic>\n              supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed that the modulatory activity of oral microbial communities varied among individuals, in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The oral microbiome is important in health and disease, and in this study, we addressed the potential role of the oral microbiome in COVID-19 infection. Our\n              <jats:italic>in vitro<\/jats:italic>\n              studies suggest that certain bacteria of the oral microbiome such as\n              <jats:italic>P. gingivalis<\/jats:italic>\n              produce compounds that could potentially inhibit SARS-CoV-2 infection. These findings elucidating the interactions between the oral microbiome and SARS-CoV-2 infection will be important in our understanding of COVID-19 pathogenesis and the development of innovative therapeutic and preventive strategies against COVID-19 infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00599-24","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T13:05:01Z","timestamp":1724159101000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of SARS-CoV-2 infection by\n            <i>Porphyromonas gingivalis<\/i>\n            and the oral microbiome"],"prefix":"10.1128","volume":"12","author":[{"given":"Alexander","family":"Bontempo","sequence":"first","affiliation":[{"name":"Department of Oral Science and Translational Research, Health Professions Division, College of Dental Medicine, Nova Southeastern University, Fort 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibel A.","family":"Antonson","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA"},{"name":"Department of Prosthodontics, Biruni University, Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Godoy","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, Health Professions Division, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank C.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Periodontology, University of Connecticut School of Dental Medicine, Farmington, Connecticut, 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