Akash Shopnil, Hossain Arafat, Mukerjee Nobendu, Sarker Md Moklesur Rahman, Khan Mohammad Firoz, Hossain Md Jamal, Rashid Mohammad A, Kumer Ajoy, Ghosh Arabinda, León-Figueroa Darwin A, Barboza Joshuan J, Padhi Bijaya Kumar, Sah Ranjit
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh.
Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
Front Pharmacol. 2023 Apr 19;14:1140494. doi: 10.3389/fphar.2023.1140494. eCollection 2023.
During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg viruses.
在新冠病毒（SARS-CoV-2）疫情的第二阶段，一种被确认为黑真菌的未知真菌感染了众多住院的新冠肺炎患者，导致死亡率上升。黑真菌与耻垢分枝杆菌、葡萄牙毛霉和米黑根毛霉等微生物有关。与此同时，其他致病疾病，如猴痘病毒和马尔堡病毒，也对全球健康产生了影响。由于这些病原体具有严重的致病能力和快速传播性，政策制定者对此表示担忧。然而，目前尚无标准疗法来管理和治疗这些疾病。由于黄连碱具有显著的抗菌、抗病毒和抗真菌特性；因此，本研究通过对黄连碱进行修饰，以确定一种针对黑真菌、猴痘病毒和马尔堡病毒的有效药物分子。在设计出黄连碱的衍生物后，对其进行了优化以获得稳定的分子结构。然后，将这些配体与从黑真菌病原体中获得的两种重要蛋白质：米黑根毛霉（PDB ID：4WTP）和耻垢分枝杆菌（PDB ID 7D6X），以及在猴痘病毒（PDB ID：4QWO）和马尔堡病毒（PDB ID 4OR8）中发现的蛋白质进行分子对接研究。分子对接之后，还进行了其他计算研究，如ADMET、QSAR、药物相似性、量子计算和分子动力学研究，以确定它们作为抗真菌和抗病毒抑制剂的潜力。对接分数表明它们对黑真菌、猴痘病毒和马尔堡病毒具有很强的亲和力。然后，进行分子动力学模拟以确定它们在含有水的生理系统中100纳秒时间内的稳定性和持久性，结果表明上述药物在模拟时间内是稳定的。因此，我们的研究提供了一份初步报告，即黄连碱衍生物对黑真菌、猴痘病毒和马尔堡病毒是安全且可能有效的。因此，黄连碱衍生物可能是开发针对黑真菌、猴痘和马尔堡病毒药物的潜在候选物。
