Neutralization of SARS-CoV-2 Spike Pseudotyped Viruses Using Postbiotic Preparations from

Background: Despite the presence of SARS-CoV-2 antivirals, namely, remdesivir, nirmatrelvir and toremifene, these drugs entail adverse effects and limited effectiveness. Thus, development of a safer alternative is imperative, and likely candidates include the cell-free supernatant (CFS) and protein fractions from Objectives: The study determined the Methods: A quasi-experimental approach was utilized in the study. Plantaricins were screened for safety Results: Plantaricins interact stably with RBD than ACE2 which were mediated by hydrogen, hydrophobic and covalent bonds. The activities of the CFS and fractions were substantially higher against the nCoV-S-EGFP BA.4/5 variant. The 1:8 dilution of CFS entailed no cytotoxicity and displayed higher activities than toremifene. Metabolomics has identified a relatively abundant putative peptide, followed by organic acids and cyclic peptides. Conclusion: Plantaricins can prevent SARS-CoV-2 entry by interacting with key RBD mutations or with intrinsically disordered RBD residues. The cationic and hydrophobic RBD mutations in the BA.4/5 variant may facilitate interactions with the putative peptide from the CFS and fractions, hence the observed potent activities. These findings can be used as basis for the development of an alternative antiviral targeting the RBD of live or pseudotyped SARS-CoV-2 variants.