Timotheous Rimsha, Naz Habiba, Arif Usman, Dar Momna Toqeer, Sarwar Muhammad Farhan, Awan Mudassar Fareed, Ali Sajed, Rab Safia Obaidur
Department of Biotechnology, Knowledge Unit of Science (KUSC), University of Management and Technology (UMT) Sialkot Campus, Sialkot, Pakistan.
Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
BMC Infect Dis. 2025 Jan 6;25(1):24. doi: 10.1186/s12879-024-10400-5.
Candida lusitaniae is one of the fungal species which causes serious health illnesses including peritonitis, vaginitis and fungemia, among others. Several antifungal drugs have been designed to tackle its infections but their efficacy is still questionable due to their associated side effects. Hence, there is a need to design those drugs which possess comparatively higher degree of therapeutic potential. Phytochemicals were selected in this regard because these compounds which satisfactorily follow this criteria as, their therapeutic index is comparatively larger than the synthetic drugs. Considering this fact, different phyto-compounds were opted in this research work to estimate their therapeutic efficiency against the secreted aspartyl proteinase (SAP) of C. lusitaniae since, it assists this pathogen in developing the infections. Initially, the structure of SAP was modelled for subsequent docking analysis. The results of molecular docking suggested that three compounds, opelconazole, daidzin 4'0-glucuronide and naringin exhibited better docking scores. Afterwards, ADME analysis of all these four compounds was performed to comprehend their drug-likeness attributes. The results of ADME analysis revealed that only the daidzin 4'0-glucuronide followed all the required parameters. Lastly, MD simulations were conducted in which top three compounds in context of docking scores along three approved anti-fungal drugs in complex with SAP were incorporated for the comparative analysis. The overall results of MD simulations suggested that daidzin 4'0-glucuronide exhibited comparatively better results. This outcome indicated that this particular compound not only showed better binding affinity with SAP during docking analysis and fulfilled all of the drug-likeness moieties among other compounds but also, displayed better simulation results, leading to a conclusion that daidzin 4'0-glucuronide could be a potential drug candidate against C. lusitaniae. However, its real-time efficacy could only be validated in clinical settings.
葡萄牙念珠菌是可引发严重健康疾病的真菌物种之一，这些疾病包括腹膜炎、阴道炎和真菌血症等。已经设计了几种抗真菌药物来应对其感染，但由于它们的相关副作用，其疗效仍然存疑。因此，需要设计具有相对较高治疗潜力的药物。在这方面选择了植物化学物质，因为这些化合物令人满意地符合这一标准，因为它们的治疗指数比合成药物相对更大。考虑到这一事实，本研究工作选择了不同的植物化合物来评估它们对葡萄牙念珠菌分泌的天冬氨酸蛋白酶（SAP）的治疗效果，因为它有助于这种病原体引发感染。最初，对SAP的结构进行建模以便后续进行对接分析。分子对接结果表明，三种化合物，奥普康唑、大豆苷4'0 - 葡萄糖醛酸苷和柚皮苷表现出更好的对接分数。之后，对所有这四种化合物进行了ADME分析以了解它们的类药属性。ADME分析结果表明，只有大豆苷4'0 - 葡萄糖醛酸苷符合所有所需参数。最后，进行了分子动力学模拟，其中将对接分数排名前三的化合物与三种已批准的抗真菌药物与SAP的复合物一起纳入进行比较分析。分子动力学模拟的总体结果表明，大豆苷4'0 - 葡萄糖醛酸苷表现出相对更好的结果。这一结果表明，这种特定化合物不仅在对接分析期间与SAP表现出更好的结合亲和力，并且在其他化合物中满足所有类药部分，而且还显示出更好的模拟结果，从而得出结论，大豆苷4'0 - 葡萄糖醛酸苷可能是一种针对葡萄牙念珠菌的潜在候选药物。然而，其实际疗效只能在临床环境中得到验证。
