{"title":"综合应用体内和体外方法鉴定针对根瘤菌孢子衣蛋白 CotH3 和高亲和力铁渗透酶 FTR1 的植物源生物活性分子","authors":"","doi":"10.1016/j.crmicr.2024.100270","DOIUrl":null,"url":null,"abstract":"<div><p><em>Rhizopus oryzae</em> is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of <em>R. oryzae</em> is essential to develop new antifungals against this fungus. Virulence factors in <em>R. oryzae</em> include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in <em>R. oryzae. In-silico</em> screening is a preferred approach to identify hit molecules for further <em>in-vitro</em> studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of <em>R. oryzae</em> and followed the Lipinski rule of drug-likeness. To corroborate the <em>in-silico</em> results, <em>in-vitro</em> studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against <em>R. oryzae</em> isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against <em>R. oryzae.</em></p></div>","PeriodicalId":34305,"journal":{"name":"Current Research in Microbial Sciences","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266651742400052X/pdfft?md5=0be4c09fe3d623d1a0dfb85a9787b401&pid=1-s2.0-S266651742400052X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Integrating In-silico and In-vitro approaches to identify plant-derived bioactive molecules against spore coat protein CotH3 and high affinity iron permease FTR1 of Rhizopus oryzae\",\"authors\":\"\",\"doi\":\"10.1016/j.crmicr.2024.100270\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>Rhizopus oryzae</em> is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of <em>R. oryzae</em> is essential to develop new antifungals against this fungus. Virulence factors in <em>R. oryzae</em> include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in <em>R. oryzae. In-silico</em> screening is a preferred approach to identify hit molecules for further <em>in-vitro</em> studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of <em>R. oryzae</em> and followed the Lipinski rule of drug-likeness. To corroborate the <em>in-silico</em> results, <em>in-vitro</em> studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against <em>R. oryzae</em> isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against <em>R. oryzae.</em></p></div>\",\"PeriodicalId\":34305,\"journal\":{\"name\":\"Current Research in Microbial Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S266651742400052X/pdfft?md5=0be4c09fe3d623d1a0dfb85a9787b401&pid=1-s2.0-S266651742400052X-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Research in Microbial Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S266651742400052X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Research in Microbial Sciences","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266651742400052X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
根霉菌是粘孢子菌病的主要致病菌之一。该病预后较差,死亡率高,对现有抗真菌药物的抗药性也令人担忧。使用抗真菌药物治疗该病比较复杂,因此,在许多病例中首选手术治疗。全面了解与 R. oryzae 的致病性相关的毒力因子对于开发针对这种真菌的新型抗真菌药物至关重要。R. oryzae 的致病因子包括细胞壁蛋白、孢子萌发蛋白和逃避宿主免疫的酶。孢子外壳蛋白(CotH3)和高亲和性铁渗透酶(FTR1)已被确定为有希望成为 R. oryzae 的治疗靶标。为进一步的体外研究确定命中分子,首选的方法是进行体内筛选。本研究在 CotH3 和 FTR1 的活性位点对接了 12 种生物活性分子。此外,对最佳对接的蛋白质-配体结构进行的分子动力学模拟分析揭示了它们在生物系统中稳定性的动力学信息。丁香酚和异丁香酚与 R. oryzae 的两个蛋白靶标都有显著的结合得分,并遵循药物相似性的 Lipinski 规则。为了证实室内研究的结果,我们使用生物活性化合物丁香酚、异丁香酚和肉豆蔻苷对从土壤样本中分离出来的 R. oryzae 进行了体外研究。丁香酚、异丁香酚的抗真菌活性为 156 µg/mL,而肉豆蔻苷的抗真菌活性为 312 µg/mL。因此,这项研究表明,丁香酚和异丁香酚可作为潜在的抗真菌分子,进一步开发其对 R. oryzae 的抗真菌活性。
Integrating In-silico and In-vitro approaches to identify plant-derived bioactive molecules against spore coat protein CotH3 and high affinity iron permease FTR1 of Rhizopus oryzae
Rhizopus oryzae is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of R. oryzae is essential to develop new antifungals against this fungus. Virulence factors in R. oryzae include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in R. oryzae. In-silico screening is a preferred approach to identify hit molecules for further in-vitro studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of R. oryzae and followed the Lipinski rule of drug-likeness. To corroborate the in-silico results, in-vitro studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against R. oryzae isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against R. oryzae.