In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinder® library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski’s rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC—ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-M^pro was found to have minimum binding energy of −10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of −8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of −63.47 ± 3 and −63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19. Communicated by Ramaswamy H. Sarma

Laccases stand out in the industrial context due to their versatile biotechnological applications. Although these enzymes are frequently investigated, currently, Pleurotus ostreatus laccase structural model is unknown. Therefore, this research aims to predict and validate a P. ostreatus laccase theoretical model by means of comparative homology. The laccase target’s primary structure (AOM73725.1) was obtained from the NCBI database, the model was predicted from homologous structures obtained from the PDB (PDB-ID: 5A7E, 2HRG, 4JHU, 1GYC) using the Swiss-Model and Modeller, and was refined in GalaxyRefine. The models were validated using PROCHECK, VERIFY 3D, ERRAT, PROVE and QMEAN Z-score servers. Moreover, molecular docking between the laccase model (Lacc4MN) and ABTS was performed on AutoDock Vina. The models that were generated by the Modeller showed superior stereochemical and structural characteristics to those predicted by the Swiss Model. The refinement made it difficult to stabilize the copper atoms which are typical of laccases. The Lacc4MN model showed the interactions between the amino acids in the active site of the laccase and the copper atoms, thereby hinting the stabilization of the metal through electrostatic interactions with histidine and cysteine. The molecular docking between Lacc4MN and ABTS showed negative free energy and the formation of two hydrogen bonds involving the amino acids ASP 208 and GLY 268, and a Pi–sulfur bond between residue HIS 458 and ABTS, which demonstrates the typical catalytic functionality of laccases. Furthermore, the theoretical model Lacc4MN presented stereochemical and structural characteristics that allow its use in silico tests. Communicated by Ramaswamy H. Sarma

Cutaneous Leishmaniasis (CL) is a neglected disease characterized by highest morbidity rates worldwide. The available treatment for CL has several limitations including serious side effects and resistance to the treatment. Herein we aimed to evaluate the activity of essential oil from the peel of Myrciaria floribunda fruits (MfEO) on Leishmania amazonensis. The cytotoxic potential of MfEO on host mammalian cells was evaluated by MTT. The in vitro leishmanicidal effects of MfEO were investigated on the promastigote and intracellular amastigote forms. The ultrastructural changes induced by MfEO were evaluated by Scanning Electron Microscopy (SEM). The molecular docking of the major compounds δ-Cadinene, γ-Cadinene, γ-Muurolene, α-Selinene, α-Muurolene and (E)–Caryophyllene onto the enzymes trypanothione reductase (TreR) and sterol 14-alpha demethylase (C14DM) were performed. Our results showed that MfEO presented moderate cytotoxicity for Vero cells and macrophages. The MfEO inhibited the growth of promastigote and the survival of intracellular amastigotes, in a dose- and time- dependent way. The MfEO presented high selectivity towards amastigote forms, being 44.1 times more toxic for this form than to macrophages. Molecular docking analysis showed that the major compounds of MfEO interact with Leishmania enzymes and that δ-Cadinene (δ-CAD) presented favorable affinity energy values over TreR and C14DM enzymes, when compared with the other major constituents. Molecular dynamics (MD) simulation studies revealed a stable binding of δ-CAD with lowest binding free energy values in MMGBSA assay. Our results suggested that δ-CAD may be a potent inhibitor of TreR and C14DM enzymes. Communicated by Ramaswamy H. Sarma

Laccase is a superfamily of ligninolytic enzymes known to degrade a wide variety of xenobiotics, including synthetic dyes. Congo Red (CR) has a diazo dye function, carcinogenic and mutagenic potential, and is currently applied in clinical analysis. The objective of this work was to produce and characterize the crude extract of Lentinus sp. in semi-solid fermentation (FSS) and perform in vitro and in silico studies to assess the potential of the crude extract to discolor the CR dye. Laccase activity was determined using ABTS as substrate and characterized. The in vitro discoloration was carried out using experimental design 2(2) at room temperature and monitored at 340 nm for 24h. Molecular docking and molecular dynamics simulations were performed between laccase and CR. The maximum laccase activity production was 29.63 U L-1 with six days of FSS. The optimal temperature and pH were 50 degrees C and 3.0, respectively. Discoloration of the CR dye was obtained only in tests containing CuSO4. Laccase formed stable complexes with the dye, presenting negative binding energy values ranging from -70.94 to -63.16 kcal mol(-1) and the occurrence of seven hydrogen bonds. Molecular dynamics results showed the stability of the system (RMSD ranging from 1.0 to 2.5 a) and protein-ligand interaction along simulation. RMSF values pointed residues at the end of chains A (residues 300 to 305, 480 to 500) and B (residues 650 to 655 and 950 to 1000) as the most flexible regions of the laccase. This study highlighted the enzymatic action in the bioremediation of CR in vitro in agreement with the in silico simulations that demonstrate the enzyme potential.Communicated by Ramaswamy H. Sarma

Rice (Oryza sativa L.) is one of the most important crops in the world, and it is considered the primary source of nutritional layout in developing countries in Asia. The glutathione S-transferases (GSTs) superfamily confers to rice protection against biotic and abiotic stress, and herbicide resistance. However, the three-dimensional structure of a GST Tau class, is unsolved. The objectives of this work were to develop a reliable comparative model for the s-transferase glutathione class Tau 4 from rice, and simulate docking interactions, against herbicides bentazon and metsulfuron. Results showed that the predicted model is reliable and has structural quality. Ramachandran plot set 91.9% of the residues in the most favored regions. All complexes showed negative binding energies values; and metsulfuron docked to the glutathione tripeptide, and it represents a possible insilico evidence of glutathione conjugation with this herbicide.

The current sweeteners available are very efficient in providing sweet taste. However, they are associated with several chronic diseases. Some glycoproteins, such as miraculins, are extremely interesting from a biotechnological point of view because they perform the bitter into sweet taste modifying function excellently, in addition to being safer as food. In contrast, purifying and synthesizing these proteins represents a major challenge for the food industry, as these proteins are large and complex molecules, which would make the final product expensive and economically unviable. In this context, emerging techniques from computational biology and molecular modelling have been promoting a remarkable revolution in protein bioengineering. Bioinspired peptides can provide many possibilities in sweeteners development through rational design. Once these peptides are smaller molecules than an entire protein, its synthesis on a large scale tends to be much easier and more economical, besides presenting a potential for better bioavailability in the organism. The techniques discussed here allow, through sophisticated pipelines and algorithms, to perform the rational design of mimetic peptides and with smaller size, which can carry out the activation of sweet taste of miraculins and to be more viable for industrial production. In this review, the premises and tools for the elaboration of synthetic peptides bioinspired in proteins with sweetening activity that mimic this action will be emphasized.Communicated by Ramaswamy H. Sarma.