Pseudomonas aeruginosa is an opportunistic human pathogen associated with cystic fibrosis. This bacterium produces, among other virulence factors, a soluble d-galactose-specific lectin PA-IL (LecA). PA-IL plays an important role in the adhesion to the host cells and is also cytotoxic. Therefore, this protein is an interesting therapeutic target, suitable for inhibition by carbohydrate-based compounds. In the current study, β-d-galactopyranoside-containing tri- and tetravalent glycoclusters were synthesized. Methyl gallate and pentaerythritol equipped with propargyl groups were chosen as multivalent scaffolds and the galactoclusters were built from the above-mentioned cores by coupling ethylene or tetraethylene glycol-bridges and peracetylated propargyl β-d-galactosides using 1,3-dipolar azide-alkyne cycloaddition. The interaction between galactoside derivatives and PA-IL was investigated by several biophysical methods, including hemagglutination inhibition assay, isothermal titration calorimetry, analytical ultracentrifugation, and surface plasmon resonance. Their ability to inhibit the adhesion of P. aeruginosa to bronchial cells was determined by ex vivo assay. The newly synthesized multivalent galactoclusters proved to be significantly better ligands than simple d-galactose for lectin PA-IL and as a result, two representatives of the dendrimers were able to decrease adhesion of P. aeruginosa to bronchial cells to approximately 32% and 42%, respectively. The results may provide an opportunity to develop anti-adhesion therapy for the treatment of P. aeruginosa infection.

Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, α-l-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of Pseudomonas aeruginosa cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras.

Pleuromutilin is a fungal diterpene natural product with antimicrobial properties, semisynthetic derivatives of which are used in veterinary and human medicine. The development of bacterial resistance to pleuromutilins is known to be very slow, which makes the tricyclic diterpene skeleton of pleuromutilin a very attractive starting structure for the development of new antibiotic derivatives that are unlikely to induce resistance. Here, we report the very first synthetic modifications of pleuromutilin and lefamulin at alkene position C19–C20, by two different photoinduced addition reactions, the radical thiol-ene coupling reaction, and the atom transfer radical additions (ATRAs) of perfluoroalkyl iodides. Pleuromutilin were modified with the addition of several alkyl- and aryl-thiols, thiol-containing amino acids and nucleoside and carbohydrate thiols, as well as perfluoroalkylated side chains. The antibacterial properties of the novel semisynthetic pleuromutilin derivatives were investigated on a panel of bacterial strains, including susceptible and multiresistant pathogens and normal flora members. We have identified some novel semisynthetic pleuromutilin and lefamulin derivatives with promising antimicrobial properties.

Objectives: Online misinformation has reached unprecedented levels during the coronavirus disease 2019 (COVID-19) pandemic. This study analyzed the magnitude and sentiment dynamics of misinformation and unverified information about public health interventions during a COVID-19 outbreak in Da Nang, Vietnam, between July and September 2020.Methods: We analyzed user-generated online information about five public health interventions during the Da Nang outbreak. We compared the volume, source, sentiment polarity, and engagements of online posts before, during, and after the outbreak using negative binomial and logistic regression, and assessed the content validity of the 500 most influential posts.Results: Most of the 54,528 online posts included were generated during the outbreak (n = 46,035; 84.42%) and by online newspapers (n = 32,034; 58.75%). Among the 500 most influential posts, 316 (63.20%) contained genuine information, 10 (2.00%) contained misinformation, 152 (30.40%) were non-factual opinions, and 22 (4.40%) contained unverifiable information. All misinformation posts were made during the outbreak, mostly on social media, and were predominantly negative. Higher levels of engagement were observed for information that was unverifiable (incidence relative risk [IRR] = 2.83; 95% confidence interval [CI], 1.33–0.62), posted during the outbreak (before: IRR = 0.15; 95% CI, 0.07–0.35; after: IRR = 0.46; 95% CI, 0.34-0.63), and with negative sentiment (IRR = 1.84; 95% CI, 1.23–2.75). Negatively toned posts were more likely to be misinformation (odds ratio [OR] = 9.59; 95% CI, 1.20–76.70) or unverified (OR = 5.03; 95% CI, 1.66–15.24).Conclusions: Misinformation and unverified information during the outbreak showed clustering, with social media being particularly affected. This indepth assessment demonstrates the value of analyzing online “infodemics” to inform public health responses.