This study aimed to identify natural bioactive compounds (NBCs) as potential inhibitors of the spike (S1) receptor binding domain (RBD) of the COVID-19 Omicron variant using computer simulations (in silico). NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening, molecular docking, molecular dynamics (MD), molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA), and molecular mechanics/generalized Born surface area (MM/GBSA). Remdesivir was used as a reference drug in docking and MD calculations. A total of 170,906 compounds were analyzed. Molecular docking screening revealed the top four NBCs with a high affinity with the spike (affinity energy <-7 kcal/mol) to be ZINC000045789238, ZINC000004098448, ZINC000008662732, and ZINC000003995616. In the MD analysis, the four ligands formed a complex with the highest dynamic equilibrium S1 (mean RMSD <0.3 nm), lowest fluctuation of the complex amino acid residues (RMSF <1.3), and solvent accessibility stability. However, the ZINC000045789238-spike complex (naringenin-4'-O glucuronide) was the only one that simultaneously had minus signal (-) MM/PBSA and MM/GBSA binding free energy values (-3.74 kcal/mol and -15.65 kcal/mol, respectively), indicating favorable binding. This ligand (naringenin-4'-O glucuronide) was also the one that produced the highest number of hydrogen bonds in the entire dynamic period (average = 4601 bonds per nanosecond). Six mutant amino acid residues formed these hydrogen bonds from the RBD region of S1 in the Omicron variant: Asn417, Ser494, Ser496, Arg403, Arg408, and His505. Naringenin-4'-O-glucuronide showed promising results as a potential drug candidate against COVID-19. In vitro and preclinical studies are needed to confirm these findings.Communicated by Ramaswamy H. Sarma.

The emergence of the new coronavirus (SARS-COV-2) is known to trigger some common diseases in humans such as pneumonia and diarrhea, the search for appropriate therapy combat COVID-19 has been intense and exhaustive. Motivation/Background: Thus, based on the rational study of drugs, a survey of potential ligands that can inhibit the vital protein in virus replication, the main protease (Mpro), has been carried out worldwide. Method: In this battle, the antiviral Remdesivir, which was created to fight the Ebola virus, proved, through the molecular anchorage, to be quite effective against its target because it presented affinity energy far superior to its co-crystallized ligand. Results: In this work, a study was carried out with Remdesivir and its derivatives, obtained in a zinc database15, to present a possible alternative, based on its structure-affinity, as potential Inhibitors of SARS-COV-2 MPro, with affinity energy ranging from -6.3 to -8.2 kcal/mol. Conclusions: It was found that both remdesivir and its diastereoisomeric derivatives have an affinity with the main protease (Mpro), responsible for viral replication, with inhibition capacity and possible alternative in its treatment.

Dengue (DENV), Zica virus (ZIKV), and Chikungunya fever (CHIK) are tropical diseases that have caused a lot of problems in general worldwide. Transmitted by mosquitoes of the species Aedes aegypti and albopictus, they have not been completely eradicated in the country, and their proliferation has only increased in the Northeast region. Within the structure of the virus, it is possible to verify the presence of glycoprotein SN1, which is responsible for its replication. If this macromolecule is inhibited using a specific or complex linker, it can interrupt its replication activity. An alternative to this problem has been using structures derived from natural products that have pharmacological properties. A dynamic and molecular docking combined study used computational simulation in the four isomeric forms of bixin against the SN1 protein. The Z,E-bixin and E,E-bixin isomers, both with affinity energy −6.7 and −6.5 Kcal/mol, presented the best results. Thus, bixin and its isomers, found in annatto seeds, maybe an initial proposal in the search for prototype compounds to study to fight this lethal virus in the future. Communicated by Ramaswamy H. Sarma

In 2023, tuberculosis (TB) once again became the leading cause of death from a single infectious agent, with 1.25 million fatalities. Current TB treatment relies on the combination of drugs with different targets of action, as monotherapies have proven less effective and promoted the rapid emergence of resistance. Transition metals play an essential role in the metabolism of Mycobacterium tuberculosis (Mtb), influencing its growth and virulence. Restriction or exposure to toxic concentrations of these metals represent host cell defense mechanisms against Mtb. This scoping review aimed to map the main protein targets involved in the transport of essential transition metals across the Mtb membrane and to assess their potential in the development of novel anti-tuberculosis agents. The review was conducted according to JBI Collaboration guidelines and reported following the PRISMA-ScR checklist. Searches were carried out in PubMed, Web of Science, and Embase for studies published up to March 2025. A total of 72 studies were included, with iron being the most investigated metal (n = 48). The mechanisms of iron influx and efflux in Mtb are relatively well characterized; however, significant knowledge gaps persist regarding the role of the ESX-3 secretion system and the translocation of siderophores across the outer membrane. For each of the 79 entries mapped, database annotation was recorded separately from the evidence demonstrated in the included studies; in 65 entries the annotated direction of transport was not demonstrated experimentally. Comparing candidates by the level of functional evidence obtained in M. tuberculosis, the evidence available from macrophage and animal infection models and the existence of alternative pathways indicate that ESX-3, IrtAB and the siderophore export platform are the most completely supported systems; no inhibitor of any of these systems is reported in the included studies.