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Background: In 1980, smallpox became the first viral disease eradicated through vaccination. After the termination of the Smallpox Eradication Program, the global immunization of the population also ceased. Now, most people do not have any immunity against infections caused by orthopoxviruses. Emerging cases of zoonotic orthopox infections transferring to humans inspire the search for new small organic molecules possessing antiviral activity against orthopoxviruses. Objective: Here, we present the synthesis and evaluation of antiviral activity against one of the orthopoxviruses, i.e., Vaccinia virus, of hybrid structures containing 1-hydroxyimidazole and benzopyranone moieties. Methods: Novel 2-(3-coumarinyl)-1-hydroxyimidazoles were synthesized. Their prototropic tautomerism was considered using 1H NMR spectroscopy. Antiviral activity of both new 2-(3-coumarinyl)- 1-hydroxyimidazoles and previously described 2-(3-chromenyl)-1-hydroxyimidazoles against Vaccinia virus was evaluated in Vero cell culture. Results: Newly synthesized 2-(3-coumarinyl)-1-hydroxyimidazoles existed in CDCl3 as a mixture of prototropic tautomers (N-hydroxyimidazole and imidazole N-oxide), transition to DMSO-d6 resulting in the prevalence of N-oxide tautomer. Evaluation of cytotoxicity and antiviral activity against Vaccinia virus was performed in Vero cell culture. Compounds possessing high antiviral activity were present in both series. It was demonstrated that the structure of heterocyclic substituent in position 2 of imidazole impacted the cytotoxicity of substances under consideration. Thus, molecules containing coumarin moiety exhibited lower toxicity than similarly substituted 2-(3-chromenyl)-1- hydroxyimidazoles. Conclusion: Perspective virus inhibiting compounds possessing antiviral activity against Vaccinia virus were revealed in the series of 2-(3-coumarinyl)-1-hydroxyimidazoles.

In this work, a library of (+)-camphor and (-)-fenchone based N-acylhydrazones, amides, and esters, including para-substituted aromatic/hetaromatic/cyclohexane ring was synthesized, with potent orthopoxvirus inhibitors identified among them. Investigations of the structure-activity relationship revealed the significance of the substituent at the para-position of the aromatic ring. Also, the nature of the linker between a hydrophobic moiety and aromatic ring was clarified. Derivatives with p-Cl, p-Br, p-CF

Purpose The aim of this work was to analyze the complete genome of probiotic bacteria Lactobacillus plantarum 8 RA 3, Lactobacillus fermentum 90 TC-4, Lactobacillus fermentum 39, Bifidobacterium bifidum 791, Bifidobacterium bifidum 1, and Bifidobacterium longum 379 and to test their activity against influenza A and SARS-CoV-2 viruses. Methods To confirm the taxonomic affiliation of the bacterial strains, MALDI TOF mass spectrometry and biochemical test systems were used. Whole genome sequencing was performed on the Illumina Inc. MiSeq platform. To determine the antiviral activity, A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798) and A/common gull/Saratov/1676/2018 (H5N6) (EPI_ISL_336925) influenza viruses and SARS-CoV-2 virus strain Australia/VIC01/2020 (GenBank: MT007544.1) were used. Results All studied probiotic bacteria are nonpathogenic for humans and do not contain the determinants of transmission-type antibiotic resistance and integrated plasmids. Resistance to antibiotics of different classes is explained by the presence of molecular efflux pumps of the MatE and MFS families. Cultures of L. fermentum 90 TC 4, L. plantarum 8 RA 3, and B. bifidum 791 showed a pronounced activity against influenza A viruses in MDCK cells. Activity against the SARS-CoV-2 virus was demonstrated only by the L. fermentum 90 TC 4 strain in VERO cells. Conclusions The studied probiotic bacteria are safe, have antiviral activity, and are of great importance for the prevention of diseases caused by respiratory viruses that can also infect the human intestine.