The aim of the studywas to analyze the genome features of the probiotic strainsBifidobacterium longum379,Bifidobacterium bifidum1, andBifidobacterium bifidum791 and study their antiviral activity.Materials and MethodsWhole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin–Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.ResultsThe genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes ofB. longum379 andB. bifidum791. A feature of theB. bifidum791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins — flavucin and lasso peptide. TheB. bifidum791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replicationin vitroup to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6·106 CFU/ml.ConclusionThe analysis of complete genomes ofB. longum379,B. bifidum1, andB. bifidum791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes ofB. longum379 andB. bifidum791 strains, in contrast toB. bifidum1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome ofB. bifidum791 strain determines its pronounced antiviral activity.