Flaviviruses are small viruses with single-stranded RNA, which include the yellow fever virus, dengue virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, and Zika virus; and are causal agents of the most important emerging diseases that have no available treatment to date. In recent years, the strategy has focused on the development of replication inhibitors of these viruses designed to act mainly by affecting the activity of enzyme proteins, such as NS3 and NS5, which perform important functions in the viral replication process. This article describes the importance of flaviviruses and the development of molecules used as inhibitors of viral replication in this genus.

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates.

(1) Introduction: Curcumin and Lippia origanoides essential oils have a broad spectrum of biological activities; however, their physicochemical instability, low solubility, and high volatility limit their therapeutic use. Encapsulation in liposomes has been reported as a feasible approach to increase the physicochemical stability of active substances, protect them from interactions with the environment, modulate their release, reduce their volatility, improve their bioactivity, and reduce their toxicity. To date, there are no reports on the co-encapsulation of curcumin and Lippia origanoides essential oils in liposomes. Therefore, the objective of this work is to prepare and physiochemical characterize liposomes loaded with the mixture of these compounds and to evaluate different in vitro biological activities. (2) Methods: Liposomes were produced using the thin-layer method and physiochemical characteristics were calculated. The antimicrobial and cytotoxic activities of both encapsulated and non-encapsulated compounds were evaluated. (3) Results: Empty and loaded nanometric-sized liposomes were obtained that are monodisperse and have a negative zeta potential. They inhibited the growth of Staphylococcus aureus and did not exhibit cytotoxic activity against mammalian cells. (4) Conclusions: Encapsulation in liposomes was demonstrated to be a promising strategy for natural compounds possessing antimicrobial activity.

Dengue is an acute febrile illness caused by the Dengue virus (DENV), with a high number of cases worldwide. There is no available treatment that directly affects the virus or the viral cycle. The objective of this study was to identify a compound derived from natural products that interacts with the NS5 protein of the dengue virus through virtual screening and evaluate its in vitro antiviral effect on DENV-2. Molecular docking was performed on NS5 using AutoDock Vina software, and compounds with physicochemical and pharmacological properties of interest were selected. The preliminary antiviral effect was evaluated by the expression of the NS1 protein. The effect on viral genome replication and/or translation was determined by NS5 production using DENV-2 Huh-7 replicon through ELISA and viral RNA quantification using RT-qPCR. The in silico strategy proved effective in finding a compound (M78) with an indole-like structure and with an effect on the replication cycle of DENV-2. Treatment at 50 µM reduced the expression of the NS5 protein by 70% and decreased viral RNA by 1.7 times. M78 is involved in the replication and/or translation of the viral genome.