RESUMEN
Colorectal cancer (CRC) is a type of cancer that occurs in the colon or rectum and kills millions of people each year. Steroid hormones are interconverted between their potent, high-affinity forms by using 17-beta hydroxysteroid dehydrogenase for their respective receptors in these tissues, with a high probability of random genetic errors. Currently, 17-beta-HSD1 studies have revealed the role of steroid metabolism in the development and proliferation of colorectal cancer. However, there is little information on how to target this enzyme with either modern medicine or natural products. In this study, we looked at 17-beta-HSD1 as a target for treating CRC development and proliferation using selected plant metabolites from previous studies. Plants are used to produce medicinal and novel bioactive compounds that are used to treat different infection. They primarily demonstrated anti-cancer effects through the regulation of cancer-related proteins, epigenetic factors and reactive oxygenase species. The study utilized Avogadro, ADMET lab 2.0, SWISS-MODEL, AutoDock, and Gromacs. Five lead molecules were chosen from a pool of plant metabolites based on their affinity for the 17-beta-HSD1 enzyme. Furthermore, two bind with high affinity are resveratrol (DG 11.29 kcal/mol) and folate (DG 12.23 kcal/mol) with low Ki values, while the rest binds with moderate affinity. Molecular dynamic simulation results also revealed that the folate-17-beta-HSD complex and reserverol- 17-beta-HSD1 complex maintained a stable conformation until the end of 100 ns. As a result, reserverol and folate could be used as lead molecules to target 17-beta-HSD1 and provide a promising starting point for further in vivo research.Communicated by Ramaswamy H. Sarma.
RESUMEN
Due to the rapid growth of the COVID-19 pandemic and its outcomes, developing a remedy to fight the predicament is critical. So far, it has infected more than 214,468,601 million people and caused the death of 4,470,969 million people according to the August 27, 2021, World Health Organization's (WHO) report. Several studies have been published on both computational and wet-lab approaches to develop antivirals for COVID-19, although there has been no success yet. However, the wet-lab approach is laborious, expensive, and time-consuming, and computational techniques have screened the activity of bioactive compounds from different sources with less effort and cost. For this investigation, we screened the binding affinity of fungi-derived bioactive molecules toward the SARS coronavirus papain-like protease (PLpro) by using computational approaches. Studies showed that protease inhibitors can be very effective in controlling virus-induced infections. Additionally, fungi represent a vast source of bioactive molecules, which could be potentially used for antiviral therapy. Fifty fungi-derived bioactive compounds were investigated concerning SARS-CoV-2 PLpro by using Auto Dock 4.2.1, Gromacs 2018. 2, ADMET, Swiss-ADME, FAF-Drugs 4.023, pKCSM, and UCLA-DOE server. From the list of the screened bioactive compounds, Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin were selected with the Auto-Dock results of -8.68, -7.52, -10.46, and -10.58 Kcal/mol, respectively, based on their binding affinity compared to the reference drug. We presented the drug likeliness, toxicity, carcinogenicity, and mutagenicity of all compounds using ADMET analysis. They interacted with the amino acid residues, Gly163, Trp106, Ser111, Asp164, and Cys270, through hydrogen bonds. The root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg) values revealed a stable interaction. From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.