Applying the bioisosterism strategy to obtain lead compounds against SARS-CoV-2 cysteine proteases: An in-silico approach.

SARS-CoV-2 cysteine proteases are essential nonstructural proteins due to their role in the formation of the virus multiple enzyme replication-transcription complex. As a result, those functional proteins are extremely relevant targets in the development of a new drug candidate to fight COVID-19. Based on this fact and guided by the bioisosterism strategy, the present work has selected 126 out of 1050 ligands from DrugBank website. Subsequently, 831 chemical analogs containing bioisosteres, some of which became structurally simplified, were created using the MB-Isoster software, and molecular docking simulations were performed using AutoDock Vina. Finally, a study of physicochemical properties, along with pharmacokinetic profiles, was carried out through SwissADME and ADMETlab 2.0 platforms. The promising results obtained with the molecules encoded as DB00549_BI_005, DB04868_BI_003, DB11984_BI_002, DB12364_BI_006 and DB12805_BI_004 must be confirmed by molecular dynamics studies, followed by in vitro and in vivo empirical tests that ratify the advocated in-silico results.

Antifungal activity evaluation of Aloe arborescens dry extract against trichosporon genus yeasts / Avaliação da atividade antifúngica do extrato seco de Aloe arborescens sobre leveduras do gênero trichosporon

The objective of this study was to investigate the antifungal activity of Aloe arborescens dry extract against Trichosporon genus yeast species. Extraction was carried out by means of a longitudinal incision in fresh leaves, which were collected on a vat, and the total volume was frozen and subsequently lyophilized. Then, 40 mg of the dry extract was dissolved in DMSO by gentle inversion in order to obtain a solution whose concentration was 4000 µg mL-1. This solution became limpid and slightly yellowish because the pigment of the latex was attenuated. It was performed serial dilutions from 2,000 to 15.625 µg mL-1 with RPMI-1640 broth. There was already no pigment in the first dilution of 2000 µg mL-1. It was analyzed fifteen strains of Trichosporon spp., and Candida albicans ATCC 10231 was used as control strain. We carried out the reading of microplates in the ELISA reader device at a wavelength of 530 nm, after incubation for 24 and 48 hours, and it was determinated the Minimum Inhibitory Concentration (MIC). The MIC50 value obtained for all Trichosporon species and for C. albicans was 500 µg mL-1. As a result, we concluded that Aloe arborescens dry extract has antifungal activity against Trichosporon yeasts.

Este trabalho teve por objetivo investigar a atividade antifúngica do extrato seco de Aloe arborescens frente a espécies de leveduras do gênero Trichosporon. A extração foi realizada por meio de uma incisão longitudinal em folhas frescas, e o volume total coletado foi congelado e, posteriormente, liofilizado. A seguir, 40 mg do extrato seco foram dissolvidos em 10 mL de DMSO por inversão deliciada para obtenção da solução-mãe a uma concentração de 4000 µg mL-1. Tal solução tornou-se límpida e levemente amarelada, pois o pigmento do látex foi atenuado. A seguir, foram efetuadas diluições seriadas de 2.000 até 15,625 µg mL-1 em caldo RPMI-1640. Na primeira diluição de 2.000 µg mL-1 já não havia mais pigmento. Quinze cepas de Trichosporon spp. foram analisadas, e Candida albicans ATCC 10231 foi empregada como cepa controle. Após incubação por 24 e 48h, foi realizada a leitura das microplacas em um aparelho leitor de ELISA no comprimento de onda de 530 nm e determinada a Concentração Inibitória Mínima (CIM). O valor de CIM50 encontrado para todas as espécies de Trichosporon analisadas e para C. albicans foi de 500 µg mL-1. Concluiu-se que o extrato seco de Aloe arborescens apresenta atividade antifúngica sobre leveduras do gênero Trichosporon.