Evaluation of interactions of silibinin with the proteins ALS3 and SAP5 against Candida albicans / Avaliação das interações da silibinina com as proteínas ALS3 e SAP5 contra Candida albicans

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.

Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.

Study of the interactions of di- and tri-terpenes from Stillingia loranthacea with the enzyme NSP16-NSP10 of SARS-CoV-2 / Estudo das interações de di- e tri-terpenos de Stillingia loranthacea com a enzima NSP16-NSP10 de SARS-CoV-2

Objective: This study aimed to evaluate the interactions of di- and tri-terpenes from Stillingia loranthacea with the enzyme NSP16-NSP10 of SARS-CoV-2, important for viral replication. Methods: The molecular docking technique was used to evaluate this interaction. Results: The analysis showed that the evaluated compounds obtained RMSD values of 0.888 to 1.944 Å and free energy of -6.1 to -9.4 kcal/mol, with the observation of hydrogen bonds, salt bridges, and pi-sulfur, pi-alkyl, and hydrophobic interactions. Conclusion: Thus, the results obtained show the potential of the compounds analyzed against the selected target. Since computer simulations are only an initial step in projects for the development of antiviral drugs, this study provides important data for future research.

Objetivo: avaliar as interações de di- e tri-terpenos de Stillingia loranthacea com a enzima NSP16-NSP10 de SARS-CoV-2, importante para a replicação viral. Métodos: A técnica de docking molecular foi utilizada para avaliar essa interação. Resultados: A análise mostrou que os compostos avaliados obtiveram valores de RMSD de 0,888 a 1,944 Å e energia livre de -6,1 a -9,4 kcal/mol, observando-se ligações de hidrogênio, pontes salinas e pi-enxofre, pi-alquil, e interações hidrofóbicas. Conclusão: Assim, os resultados obtidos mostram o potencial dos compostos analisados frente ao alvo selecionado. Como as simulações computacionais são apenas um passo inicial nos projetos de desenvolvimento de medicamentos antivirais, este estudo fornece dados importantes para pesquisas futuras.

Virtual screening based on molecular docking of lysosomotropic compounds as therapeutic agents for COVID-19 / Triagem virtual baseada no encaixe molecular de compostos lisossomotrópicos como agentes terapêuticos para COVID-19

Objective: Analyze lysosomotropic agents and their action on COVID-19 targets using the molecular docking technique. Methods: Molecular docking analyses of these lysosomotropic agents were performed, namely of fluoxetine, imipramine, chloroquine, verapamil, tamoxifen, amitriptyline, and chlorpromazine against important targets for the pathogenesis of SARS-CoV-2. Results: The results revealed that the inhibitors bind to distinct regions of Mpro COVID-19, with variations in RMSD values from 1.325 to 1.962 Å and binding free energy of -5.2 to -4.3 kcal/mol. Furthermore, the analysis of the second target showed that all inhibitors bonded at the same site as the enzyme, and the interaction resulted in an RMSD variation of 0.735 to 1.562 Å and binding free energy ranging from -6.0 to -8.7 kcal/mol. Conclusion: Therefore, this study allows proposing the use of these lysosomotropic compounds. However, these computer simulations are just an initial step toward conceiving new projects for the development of antiviral molecules.

Objetivo: aAnalisar agentes lisossomotrópicos e sua ação em alvos de COVID-19 usando a técnica de docking molecular. Métodos: Foram realizadas análises de docagem molecular destes agentes lisossomotrópicos, nomeadamente de fluoxetina, imipramina, cloroquina, verapamil, tamoxifeno, amitriptilina e clorpromazina contra alvos importantes para a patogenia do SARS-CoV-2. Resultados: Os resultados revelaram que os inibidores se ligam a regiões distintas do Mpro COVID-19, com variações nos valores de RMSD de 1.325 a 1.962 Å e energia livre de ligação de -5,2 a -4,3 kcal/mol. Além disso, a análise do segundo alvo mostrou que todos os inibidores se ligaram no mesmo sítio da enzima, e a interação resultante em uma variação de RMSD de 0,735 a 1.562 Å e energia livre de ligação variando de -6,0 a -8,7 kcal/mol. Conclusão: Portanto, este estudo permite propor o uso desses compostos lisossomotrópicos. No entanto, essas simulações em computador são apenas um passo inicial para a concepção de novos projetos para o desenvolvimento de moléculas antivirais.

Bixinoids Derived from Bixa orellana as a Potential Zika Virus Inhibitor Using Molecular Simulations. Antiviral Effect on the Zika Virus of Bixinoids

Abstract Zika fever is a viral infection of great relevance in public health, especially in tropic regions, in which there is a predominance of mosquitoes of the genus Aedes, vectors of the disease. Microcephaly in neonatal children and Guillain-Barré syndrome in adults can be caused by the action of the Zika virus (ZIKV). Non-structural proteins, such as NS2B, NS3 and NS5, are important pharmacological targets, due to their action in the life cycle. The absence of anti-Zika drugs raises new research, including prospecting for natural products. This work investigated the in silico antiviral activity of bixin and six other derived molecules against the Zika viral proteins NS2B-NS3 and NS5. The optimized structure was subjected to molecular docking to characterize the interaction between bixinoids and ZIKV non-structural proteins, where significant interactions were observed with amino acid residues in the catalytic site in each enzyme. These results suggest that bixin and ethyl bixin has the potential to interfere with the enzymatic activity of NS2B, NS3 and NS5, thus being an indication of being a promising anti-Zika agent.

Protective Effect of Quercetin on Renal Tubular Cells and the Involvement with the Renin-Angiotensin-Aldosterone Axis

Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.