In Central Eurasia, the availability of drugs that are inhibitors of the SARS-CoV-2 virus and have proven clinical efficacy is still limited. The aim of this study was to evaluate the activity of drugs that were available in Kazakhstan during the acute phase of the epidemic against SARS-CoV-2. Antiviral activity is reported for Favipiravir, Tilorone, and Cridanimod, which are registered drugs used for the treatment of respiratory viral infections in Kazakhstan. A licorice (Glycyrrhiza glabra) extract was also incorporated into this study because it offered an opportunity to develop plant-derived antivirals. The Favipiravir drug, which had been advertised in local markets as an anti-COVID cure, showed no activity against SARS-CoV-2 in cell cultures. On the contrary, Cridanimod showed impressive high activity (median inhibitory concentration 66 μg/mL) against SARS-CoV-2, justifying further studies of Cridanimod in clinical trials. Tilorone, despite being in the same pharmacological group as Cridanimod, stimulated SARS-CoV-2 replication in cultures. The licorice extract inhibited SARS-CoV-2 replication in cultures, with a high median effective concentration of 16.86 mg/mL. Conclusions: The synthetic, low-molecular-weight compound Cridanimod suppresses SARS-CoV-2 replication at notably low concentrations, and this drug is not toxic to cells at therapeutic concentrations. In contrast to its role as an inducer of interferons, Cridanimod is active in cells that have a genetic defect in interferon production, suggesting a different mechanism of action. Cridanimod is an attractive drug for inclusion in clinical trials against SARS-CoV-2 and, presumably, other coronaviruses. The extract from licorice shows low activity against SARS-CoV-2. At the same time, high doses of 2 g/kg of this plant extract show little or no acute toxicity in animal studies; for this reason, licorice products can still be considered for further development as a safe, orally administered adjunctive therapy.
Monitoring poultry microbiota and antimicrobial resistance genes is important, as they can reflect flock health, farm conditions, and the level of antimicrobial resistance. Although shotgun metagenomics has been widely applied worldwide to investigate poultry microbiota and antimicrobial resistance, comparable baseline datasets describing the cloacal microbiota and resistome of poultry in Kazakhstan are scarce. In this study, taxonomic and resistome profiles were characterized in pooled metagenomes of the cloacal microbiota of chickens sampled from household and industrial poultry farms in Kazakhstan. Cloacal swabs were collected from laying hens, pooled at the house level, and analyzed using high-throughput metagenomic sequencing. Taxonomic profiles were generated at the genus level, and antimicrobial resistance gene signals were summarized by drug class. Compositional patterns were assessed using CLR/Aitchison ordination, the Mantel test, and Procrustes analysis. The pooled samples exhibited heterogeneous microbiota profiles at the genus level and included taxa of veterinary interest, such as Chlamydia, Avibacterium, and Gallibacterium spp. Resistome profiling revealed a broad but uneven distribution of antimicrobial resistance signals, including those associated with tetracyclines, fluoroquinolones, aminoglycosides, and beta-lactams. Taxonomic and resistome profiles showed preliminary alignment at the matrix level, indicating that resistome variations are partially linked to microbial community structure.