Department of Biotechnology, School of Chemical & Biotechnology, SASTRA Deemed University, Thanjavur, India.
Centre for Bioenergy, SASTRA Deemed University, Thanjavur, India.
J Biomol Struct Dyn. 2023;41(24):15386-15399. doi: 10.1080/07391102.2023.2188960. Epub 2023 Mar 16.
The fungi, cause major infections such as cryptococcal meningitis and cryptococcosis. Therefore, we explored the use of Thioredoxin reductase (Trr1) from as a gene target for the development of novel antifungal agents. Trr1 plays an essential role in the survival in the oxidative environment of macrophages and is important for the virulence of . During the thermochemical conversion (pyrolysis) of lignocellulosic biomass (LCB), a cocktail of compounds is produced by the decomposition and degradation. In general, LCB-derived cocktail of compounds is a rich source of aromatic compounds that have been shown to be antifungal in nature. Usually, the aqueous phase produced during biomass pyrolysis is generally regarded as waste. Here, we used biomass as the antifungal source and obtained the aqueous phase after pyrolysis. Using GC-MS analysis of the aqueous phase collected from biomass revealed the presence of a large number of aromatic and organic compounds. Using virtual screening, the compounds present in the aqueous phase were docked against Trr1 using GLIDE. Two promising candidates were analyzed further by performing molecular dynamics simulation using GROMACS, to establish stable interactions. We validated the computational results with clustering analysis. We report that 2,4-Di-tertbutyl phenol and 1H-Pyrazole, 4-ethyl-3,5-dimethyl have a potent antifungal property and we postulate that they could be a potent antifungal agent against Trr1 of
真菌会引起重大感染，如隐球菌性脑膜炎和隐球菌病。因此，我们探索了使用来自 的硫氧还蛋白还原酶 (Trr1) 作为开发新型抗真菌药物的基因靶标。Trr1 在巨噬细胞氧化环境中的存活中发挥着重要作用，对于 的毒力也很重要。在木质纤维素生物质 (LCB) 的热化学转化（热解）过程中，通过分解和降解会产生一组化合物。一般来说，LCB 衍生的化合物混合物是具有天然抗真菌特性的芳香族化合物的丰富来源。通常，生物质热解过程中产生的水相通常被视为废物。在这里，我们使用 生物质作为抗真菌源，并获得热解后的水相。使用 GC-MS 对从 生物质收集的水相进行分析，发现存在大量的芳香族和有机化合物。使用虚拟筛选，使用 GLIDE 将水相中存在的化合物对接 Trr1。通过使用 GROMACS 进行分子动力学模拟进一步分析了两个有前途的候选物，以建立稳定的相互作用。我们使用聚类分析验证了计算结果。我们报告 2,4-二叔丁基苯酚和 1H-吡唑，4-乙基-3,5-二甲基具有很强的抗真菌特性，我们推测它们可能是针对 Trr1 的有效抗真菌药物。
