Dengue virus (DENV) threatens global health; specific antiviral drugs are required to combat it. Such anti-DENV therapeutics can be rapidly developed by repositioning the drugs approved for other indications. This study investigated six medications of different classes drawn from a library of molecules. In silico analyses were performed to determine potential binding affinity for the DENV non-structural protein NS3 protease and NS5 RNA-dependent RNA polymerase (RdRp). Of the six candidates, galidesivir and tadalafil showed the highest binding affinities for the DENV NS3 protease and NS5 RdRp, with tadalafil demonstrating the highest binding affinity. Galidesivir and tadalafil substantially suppressed viral replication in DENV replicon cells without inducing cytotoxicity and showed half-maximal inhibitory concentrations of 10 μM and 2.56 μM, respectively. Both galidesivir and tadalafil effectively suppress DENV infection in human hepatoma and baby hamster kidney cells, and tadalafil demonstrates protease-inhibitory activity. In an AG129 mouse model of DENV infection, both galidesivir and tadalafil reduced viral loads in the serum, with tadalafil producing a notable reduction by day four. Both drugs markedly suppressed DENV replication in the hepatic tissue. Histopathologically, both galidesivir- and tadalafil-treated mice showed alleviation of DENV-induced lesions in the spleen and liver, indicating the potential therapeutic effects of these drugs. These findings highlight the potential of repositioning galidesivir and tadalafil as effective anti-DENV therapies with low cytotoxicity, meeting the urgent global need for new therapeutic agents against this pathogen.

A cross-sectional study was conducted to investigate the prevalence and antimicrobial resistance pattern in Salmonella from 108 rectal swab of stray dogs of 9 randomly selected areas of Chittagong Metropolitan Area. Rectal swabs were collected for isolating Salmonella enterica serovar Typhimurium through bacteriological culture and InvA specific PCR assay followed by antimicrobial susceptibility testing. Out of the 108 samples, females showed higher prevalence (66.67%) than males (58.93%). Among the 67 bacterial culture positive isolates, 10.45% was Salmonella Typhimurium in InvA gene specific PCR. Isolated Salmonella was tested for resistance to twelve different antimicrobial agents, using disc diffusion method. In cultural sensitivity test, 100% resistance was found against Amoxicillin where higher resistance was found against Azithromycin, Cefixime, Ampicilin and Pefloxacin. Gentamycin and Colistin appeared to be sensitive. Multidrug resistance of Salmonella spp. has increased with a great deal in developing countries in the last decades. In this study, most of the Salmonella isolates were multidrug resistant. Rational use of antibiotics needs to be adopted in clinical practice to prevent the emergence of multi-drug resistance Salmonella and their zoonotic transmission.

Lactic acid bacteria play a crucial role in fermented food production and serve as important sources of antimicrobial peptides. This study reports four lactic acid bacteria strains isolated from fermented chicken meat, which harbor biosynthetic gene clusters encoding antimicrobial compounds. These strains are classified within the genera Pediococcus and Lactiplantibacillus .

Background: Hepatitis B virus (HBV) is a major cause of morbidity and mortality globally, and chronic infections are associated with cirrhosis and hepatocellular carcinoma. Issues with conventional treatments and vaccines mean there is a need for new therapeutic vaccines, which must elicit a strong and sustainable immune response. Here, we evaluated the immunogenicity of dual-antigen vaccines containing hybrid surface (hy-LHBs) and core (HBc) antigens, combined with a carboxyl-vinyl polymer (CVP) as a mucoadhesive excipient, following intranasal administration in mice. Methods: Mice were intranasally administered a mixed vaccine (10 µg of hy-LHBs and 2.5 or 10 µg of HBc) with or without a CVP excipient, and they were assessed for their immune response (levels of IgGs or IgA antibodies in an ELISA, IFN-γ level in splenocytes in an ELISpot assay, and cytokine/chemokine levels in a BioPlex assay). A protein stability assay was also conducted for vaccine formulations with and without excipients. Results: Significantly enhanced IgG production was noted targeting hy-LHBs and (less markedly) HBc at 10 µg/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 µg HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1α (#00, #00-07, 0B), and MCP-1 (#00-07, 0B) in mice that received treatment compared to those of untreated mice. The endpoint titers of IgG1 and IgG2a were measured, which were higher with CVP excipients than without. From the IgG2a/IgG1 ratio, a higher IgG1 response was induced by CVPs to hy-LHBs and a higher IgG2a response was induced to HBc. Th2-dominant phenotype to hy-LHBs was induced with CVP#00 in an ELISpot assay. The highest anti-hy-LHBs antibody titer was noted with the conventional CVP#00 excipient. Consistent with these results, a higher amount of neutralizing antibodies of HBV was induced with CVP#00 treatment and followed by #00-03 and #14-00. Conclusions: We consider that the addition of CVP excipients to vaccine formulation enhances immunogenicity and HBV antigen stability for intranasal vaccines. This effect was seen for both humoral and cell-mediated immune responses, indicating the potential of CVPs as excipients in intranasal HBV vaccines.

Lactic acid bacteria play a crucial role in fermented food production and serve as important sources of antimicrobial peptides. This study reports four lactic acid bacteria strains, isolated from fermented chicken meat, which harbor biosynthetic gene clusters encoding antimicrobial compounds. These strains are classified within the genera Pediococcus and Lactiplantibacillus .