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Abstract Scientists and researchers have been searching for drugs targeting the main protease (Mpro) of SARS-CoV-2, which is crucial for virus replication. This study employed a virtual screening based on molecular docking to identify benzoylguanidines from an in-house chemical library that can inhibit Mpro on the active site and three allosteric sites. Molecular docking was performed on the LaSMMed Chemical Library using 88 benzoylguanidine compounds. Based on their RMSD values and conserved pose, three potential inhibitors (BZG1, BZG2, and BZG3) were selected. These results indicate that BZG1 and BZG3 may bind to the active site, while BZG2 may bind to allosteric sites. Molecular dynamics data suggest that BZG2 selectively targets allosteric site 3. In vitro tests were performed to measure the proteolytic activity of rMpro. The tests showed that BZG2 has uncompetitive inhibitory activity, with an IC50 value of 77 µM. These findings suggest that benzoylguanidines possess potential as Mpro inhibitors and pave the way towards combating SARS-Cov-2 effectively.

Staphylococcus aureus is a causative agent of nosocomial infections and its antibiotic-resistant strains give cause for concern. Solutions are being explored to improve treatment for these infections, including repositioning drugs such as statins and using nanoparticles with antimicrobial properties. This study evaluated the antimicrobial effects of simvastatin (SIM) and biologically synthesized silver nanoparticles (bio-AgNPs) in isolate form and in combination using assays of minimum inhibitory concentration (MIC), an in vitro biofilm model, and the association of antimicrobials against clinical strains of S. aureus. Bio-AgNPs showed a 53.8 ± 1.23 nm mean diameter and standard deviation, a 0.23 polydispersity index, and a −25.66 ± 2.19 mV mean potential and standard deviation. Transmission electron microscopy confirmed the formation of nanoparticles, and the presence of Ag0 and AgCl. S. aureus strains were sensitive to bio-AgNPs and SIM, showing 31.88–187.5 and 74.66–149.32 μM concentrations, respectively. The association assay showed 2.0 fractional inhibitory concentration indices (i.e., indifferent for clinical strains) and 0.32 values for the standard ATCC 29213 strain (synergy). Biofilm inhibition assays with isolated SIM and bio-AgNPs showed decreased biofilm formation 4× to ⅛ MICs concentrations, showing no synergism in association. These findings evince that simvastatin and bio-AgNPs at subinhibitory concentrations can serve as antimicrobial agents against S. aureus biofilm.

Onychomycosis is a common fungal nail infection for which new antifungals are needed to overcome antimicrobial resistance and the limitations of conventional treatments. This study reports the development of antifungal nail lacquers containing oregano essential oil (OEO), rosemary essential oil (REO), and biogenic silver nanoparticles (bioAgNPs). The formulations (F) were tested against dermatophytes using agar diffusion, ex vivo nail infection, and scanning electron microscopy techniques. They were evaluated for their pharmacotechnical characteristics and by FTIR-PAS to assess permeation across the nail. F-OEO and F-OEO/bioAgNPs were promising candidates for the final nail lacquer formulation, as they permeated through the nail and showed antifungal efficacy against dermatophytes-contaminated nails after 5 days of treatment. Treated nails exhibited decreased hyphae and spores compared to the untreated control; the hyphae were atypically flattened, indicating loss of cytoplasmic content due to damage to the cytoplasmic membrane. The formulations were stable after centrifugation and thermal stress, maintaining organoleptic and physicochemical characteristics. Both F-OEO and F-OEO/bioAgNPs had pH compatible with the nail and drying times (59–90 s) within the reference for nail lacquer. For the first time, OEO and bioAgNPs were incorporated into nail lacquer, resulting in a natural and nanotechnological product for onychomycosis that could combat microbial resistance.

Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from Anadenanthera colubrina (Vell.) Brenan var. colubrina. The methodology included obtaining the extract and characterizing the AgNPs, which revealed antimicrobial activity against MDR bacteria. A. colubrina species is valued in indigenous and traditional medicine for its medicinal properties. Herein, it was employed to synthesize AgNPs with effective antibacterial activity (MIC = 19.53–78.12 μM) against clinical isolates from the ESKAPEE group, known for causing high hospitalization costs and mortality rates. Despite its complexity, AgNP synthesis is an affordable method with minimal environmental impacts and risks. Plant-synthesized AgNPs possess unique characteristics that affect their biological activity and cytotoxicity. In this work, A. colubrina bark extract resulted in the synthesis of nanoparticles measuring 75.62 nm in diameter, with a polydispersity index of 0.17 and an average zeta potential of −29 mV, as well as low toxicity for human erythrocytes, with a CC50 value in the range of 961 μM. This synthesis underscores its innovative potential owing to its low toxicity, suggesting applicability across several areas and paving the way for future research.

The green synthesis of silver nanoparticles (AgNPs) can be developed using safe and environmentally friendly routes, can replace potentially toxic chemical methods, and can increase the scale of production. This study aimed to synthesize AgNPs from aqueous extracts of guarana (Paullinia cupana) leaves and flowers, collected in different seasons of the year, as a source of active biomolecules capable of reducing silver ions (Ag+) and promoting the stabilization of colloidal silver (Ag0). The plant aqueous extracts were characterized regarding their metabolic composition by liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS/MS), phenolic compound content, and antioxidant potential against free radicals. The synthesized AgNPs were characterized by UV/Vis spectrophotometry, dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and scanning electron microscopy coupled to energy-dispersive X-ray spectrometry (EDX). The results demonstrated that the chemical characterization indicated the presence of secondary metabolites of many classes of compounds in the studied aqueous extracts studied, but alkaloids and flavonoids were predominant, which are widely recognized for their antioxidant capabilities. It was possible to notice subtle changes in the properties of the nanostructures depending on parameters such as seasonality and the part of the plant used, with the AgNPs showing surface plasmon resonance bands between 410 and 420 nm using the leaf extract and between 440 and 460 nm when prepared using the flower extract. Overall, the average hydrodynamic diameters of the AgNPs were similar among the samples (61.98 to 101.6 nm). Polydispersity index remained in the range of 0.2 to 0.4, indicating that colloidal stability did not change with storage time. Zeta potential was above −30 mV after one month of analysis, which is adequate for biological applications. TEM images showed AgNPs with diameters between 40.72 to 48.85 nm and particles of different morphologies. EDX indicated silver content by weight between 24.06 and 28.81%. The synthesized AgNPs exhibited antimicrobial efficacy against various pathogenic microorganisms of clinical and environmental interest, with MIC values between 2.12 and 21.25 µg/mL, which is close to those described for MBC values. Therefore, our results revealed the potential use of a native species of plant from Brazilian biodiversity combined with nanotechnology to produce antimicrobial agents.