COMVSVIR

Commensals vs viruses: evolutionary shaped antiviral compounds produced by the nasopharyngeal microbiota

01/04/2024 to 31/03/2027

In our approach, termed “Commensals versus Viruses”, we exploit the fact that commensals reside in the nasopharyngeal tract, the major entry portal for the transmission of respiratory and many other viruses. As such, they may have evolved to confer specific selection advantages, i.e., protection from viral infection, to their human host by directly producing antiviral agents or metabolites. This approach already considers, even at the screening stage, important forthcoming questions for drug development, e.g., compound safety, formulation, administration and stability. Since the compounds originate from human commensal bacteria, these properties probably arose through co-evolution. Therefore, we can expect such compounds to have low toxicity, to be applied in a topical formulation in the nasal cavity (for instance, as a spray) and to be stable at 37°C. During the pilot phase, extracts from more than 600 cultured commensal bacterial strains were prepared and screened for antiviral activity against SARS-CoV-2. Among them, extracts from commensal Staphylococcus epidermidis, one of the most abundant bacterial species present in the nasal microbiota, efficiently blocked SARS-CoV-2 infections. Analysis of this extracts via mass spectrometry identified a peptide of approximately 25 amino acids. A purified sample of this peptide exerted strong antiviral activity against SARS-CoV-2, FluAV and RSV in vitro. We have determined the chemical structure of this bacterial product, a unique peptide related to delta- hemolysin, and named it “Respiratory Viruses Blocking Peptide” (RVBP).