RESUMEN

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in the high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyzes, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, liver receptors X α and ß, as well as peroxisome proliferator-activated receptors α and γ. In this study, for the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Asunto(s)

Simulación del Acoplamiento Molecular , Cebollas , Polifenoles , Cebollas/química , Polifenoles/farmacología , Humanos , Ligandos , Suplementos Dietéticos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo

RESUMEN

Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.

Asunto(s)

COVID-19/prevención & control , Antivirales/química , Antivirales/uso terapéutico , Productos Biológicos/uso terapéutico , COVID-19/patología , COVID-19/terapia , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Síndrome de Liberación de Citoquinas/prevención & control , Diseño de Fármacos , Reposicionamiento de Medicamentos , Humanos , Inmunoterapia , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/fisiología

RESUMEN

Computational chemistry simulations are extensively used to model natural phenomena. To maintain performance similar to molecular mechanics, but achieve comparable accuracy to quantum mechanical calculations, many researchers are using hybrid QM/MM methods. In this article we evaluate our GPU-accelerated ONIOM implementation by measurements on the crambin and HIV integrase proteins with different size QM model systems. We demonstrate that by using a larger QM region, a better energy accuracy can be achieved at the expense of simulation time. This trade-off is important to consider for the researcher running QM/MM calculations. Furthermore, we show that the ONIOM energy monotonically approaches the pure quantum mechanical energy of the whole system. The experiments are made feasible by utilizing the cutting-edge BrianQC quantum chemistry module for Hartree-Fock level SCF and our GPU-accelerated MMFF94 force field implementation for molecular mechanics calculations.

Asunto(s)

Simulación de Dinámica Molecular , Teoría Cuántica , Modelos Biológicos , Proteínas

RESUMEN

This article addresses two research questions related to reproducibility within the context of research related to computer science. First, a survey on reproducibility addressed to researchers in the academic and private sectors is described and evaluated. The survey indicates a strong need for open and easily accessible results, in particular, reproducing an experiment should not require too much effort. The results of the survey are then used to formulate guidelines for making research results reproducible. In addition, this article explores four approaches based on software tools that could bring forward reproducibility in research results. After a general analysis of tools, three examples are further investigated based on actual research projects which are used to evaluate previously introduced tools. Results indicate that the evaluated tools contribute well to making simulation results reproducible but due to conflicting requirements, none of the presented solutions fulfills all intended goals perfectly.