Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome

The COVID-19 pandemic persists despite the availability of vaccines, and it is, therefore, crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effectexerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis 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. Unidentifiedfactors present in P. gingivalis 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 findingscontribute to our understanding of the complex relationship between the oral microbiome and viral infections, offeringpotential avenues for innovative therapeutic strategies in combating COVID-19.