Background The sanitary emergency installed in the world, generated by the pandemic of COVID-19, instigates the search for scientific strategies to mitigate the damage caused by the disease to different sectors of society. The disease caused by the coronavirus, SARS-CoV-2, reached 216 countries/territories, where about 199 million people were reported with the infection. Of these, more than 4 million died. In this sense, strategies involving the development of new antiviral molecules are extremely important. The main protease (Mpro) from SARS-CoV-2 is an important target, which has been widely studied for antiviral treatment. This work aims to perform a screening of pharmacodynamics and pharmacokinetics of synthetic hybrids from thymoquinone and artemisin (THY-ART) against COVID-19. Results Molecular docking studies indicated that hybrids of artemisinin and thymoquinone showed a relevant interaction with the active fraction of the enzyme Mpro, when compared to the reference drugs. Furthermore, hybrids show an improvement in the interaction of substances with the enzyme, mainly due to the higher frequency of interactions with the Thr199 residue. ADMET studies indicated that hybrids tend to permeate biological membranes, allowing good human intestinal absorption, with low partition to the central nervous system, potentiation for CYP-450 enzyme inhibitors, low risk of toxicity compared to commercially available drugs, considering mainly mutagenicity and cardiotoxicity, low capacity of hybrids to permeate the blood–brain barrier, high absorption and moderate permeability in Caco-2 cells. In addition, T1–T7 tend to have a better distribution of their available fractions to carry out diffusion and transport across cell membranes, as well as increase the energy of interaction with the SARS-CoV-2 target. Conclusions Hybrid products of artemisinin and thymoquinone have the potential to inhibit Mpro, with desirable pharmacokinetic and toxicity characteristics compared to commercially available drugs, being indicated for preclinical and subsequent clinical studies against SARS-CoV-2. Emphasizing the possibility of synergistic use with currently used drugs in order to increase half-life and generate a possible synergistic effect. This work represents an important step for the development of specific drugs against COVID-19.

COVID-19 pandemic is the biggest public health problem of the century so far.The main protease (Mpro) is one of the main enzymes studied as a pharmacological target. In this context, the present work aimed to perform a virtual screening of possible inhibitors against the enzyme Mpro, having limonoids as the main object of research as supposed inhibitors. Molecular docking simulations indicated that limonoids have an affinity to complex with M-pro.However, Limonine and Nimoliciol showed nonspecific and low affinity interactions. In conclusion, Limonoids are substances of natural origin that can be used in the study of new pharmacological tools designed to combat and understand COVID-19.

Clitoria fairchildiana is a common plant in Amazon rain forest. Popularly known as sombreiro, this plant has a great potential to use its phytochemical content for biological and medical applications. Stemonal, one of many phytochemical products extracted from "sobreiro", presents cytotoxic and anti-inflamatory activities, which means that has great potential for pharmaceutical applications. In order to collaborate with stemonal research, this paper studied the molecular properties of this molecule. The molecular structure of stemonal was optimized using semi-empiric methods, such as PM3, using ArgusLab® software. Molecular parameters, such as frontier orbitals (HOMO and LUMO), MESP and formation enthalpy were obtained. Also, molecular docking experiments were conducted in order to evaluate the applicability over AChE, and the coupling of stemonal in this enzyme shows that the phytochemical binds into the catalytic site of the enzyme, which means that the molecule inhibits the hydrolysis of acethylcoline, the neurotransmitter evolved into skeletal muscules. Therefore, stemonal molecule has great potential to be applied into pharmaceutical formulations to achieve a better treatment for Alzheimer's diesease.

Chagas disease caused by Trypanosoma cruzi, which affects thousands of people around the world. In recent years, research aimed at the discovery of new drugs has started to seek specific macromolecular targets for the disease. In this context, enzymes are therapeutic targets of great interest, since they play a fundamental role in many diseases. In this context, the present work aimed to characterize the Machilin G molecule conformationally and evaluate its interactions in the main therapeutic targets involved in the replication of T. cruzi. To understand the inhibitory mechanism of Machilin G on the evolutionary forms of T. cruzi, the molecule it was conformationally characterized, until reaching thermodynamic stability, and then it was submitted to molecule docking routines, having as protein targets the Cruzain enzymes, Tripanothione reductase and glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH). Machilin G had its structure optimized using semi-empirical quantum calculations, through this technique it was possible to generate the thermodynamically more stable conformation. Through the method of analysis of the computer simulations of molecular anchoring, it was demonstrated that the ligand Machilin G was coupled to the active site of the enzyme TcGAPDH, at distances close to the chalepin. In relation to Cruzain, it is possible to highlight that the ligand Machilin G does not interact with the amino acids of the active site of the enzyme, being at a considerable distance in relation to the ligand KB2. Regarding the enzyme Trypanothione reductase, the ligand Machilin G had few interactions with the amino acids of the active site. The intermolecular interactions found for the complex formed and the values obtained at a distance from the enzyme residues indicate that Machilin G has potential application as a new inhibitor of the enzyme Trypanosoma cruzi TcGAPDH. The present work being a fundamental step for the understanding of Machilin G mechanism of action in view of the evolutionary forms of the t-cruzi parasite.

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