BACKGROUND Owing to increased spending on pharmaceuticals since 2010, discussions about rising costs for the development of new medical technologies have been focused on the pharmaceutical industry. Computational techniques have been developed to reduce costs associated with new drug development. Among these techniques, virtual high-throughput screening (vHTS) can contribute to the drug discovery process by providing tools to search for new drugs with the ability to bind a specific molecular target. OBJECTIVES In this context, Brazilian malaria molecular targets (BraMMT) was generated to execute vHTS experiments on selected molecular targets of Plasmodium falciparum. METHODS In this study, 35 molecular targets of P. falciparum were built and evaluated against known antimalarial compounds. FINDINGS As a result, it could predict the correct molecular target of market drugs, such as artemisinin. In addition, our findings suggested a new pharmacological mechanism for quinine, which includes inhibition of falcipain-II and a potential new antimalarial candidate, clioquinol. MAIN CONCLUSIONS The BraMMT is available to perform vHTS experiments using OCTOPUS or Raccoon software to improve the search for new antimalarial compounds. It can be retrieved from www.drugdiscovery.com.br or download of Supplementary data.

The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001) against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC) were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol). The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2) and a human cell line (WI-26VA4). Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM) and inactive against WI-26VA4 (IC50 > 200 µM). Further ligand optimisation cycles generated new prospects for docking and biological assays.

Avaliou-se o efeito de diferentes formas de processamento da casca de mandioca na alimentação sobre o desempenho e as características de carcaça, a morfologia ruminal e a viabilidade técnico-econômica da criação de ovinos. Foram utilizados 20 ovinos machos da raça Santa Inês, desmamados, com peso inicial de 19,02±0,21 kg e 90 dias de vida. O delineamento experimental foi inteiramente casualizado com cinco repetições por dieta. Durante o período experimental de 84 dias, incluindo 14 dias de adaptação, os animais foram mantidos em sistema de semiconfinamento em pastagem de Brachiaria decumbens. Foram avaliadas quatro formas de processamento da casca de mandioca: desidratada triturada em peneira de 12 ou de 5 mm; úmida triturada e ensilada; e úmida triturada e hidrolisada com 0,5% de cal virgem (óxido de cálcio - CaO). O peso médio ao abate foi 30,72±1,46 kg. Não houve influência do tipo de processamento da casca sobre as características de desempenho analisadas, as características quantitativas de carcaça e a morfologia ruminal, sendo influenciado somente o rendimento de paleta. A casca de mandioca hidrolisada foi a que promoveu melhor eficiência econômica. Os tipos de processamento da casca de mandioca não alteram o desempenho, as características de carcaça, os rendimentos de corte e a morfologia ruminal dos ovinos Santa Inês.

The objective of this trial was to evaluate the effect of different forms of processing of cassava peel in sheep feeding on performance traits, carcass, morphology and rumen and economic technical feasibility. Twenty non-castrated male Santa Ines lambs of 19.02±0.21 kg of initial body weight and 90 days of age at the beginning of the study were used in this trial. The design was completely randomized design with five replications per treatment. During the experimental period of 84 days, including 14 days of adaptation, animals were kept in semi-confinement on Brachiaria decumbens. Four forms of cassava peel processing were evaluated: dried cassava peel ground through 12-mm sieve; dried cassava peel ground through 5-mm sieve; ground and ensiled cassava peel, and wet, ground hydrolyzed with 0.5% lime (calcium oxide - CaO). The average weight at slaughter was 30.72±1.46 kg. There was no influence of the type of processing on the performance variables analyzed, quantitative carcass characteristics or ruminal morphology; only the values of width and leg yield palette were influenced. Hydrolyzed cassava peel showed the best economic efficiency between treatments. The different methods of processing cassava peel do not affect performance, carcass characteristics, yield cuts or rumen morphology of Santa Ines sheep.