Cherif Aziza, Basharat Zarrin, Yaseen Muhammad, Bhat Mashooq Ahmad, Uddin Imad, Ziedan Noha I, Mabood Fazal, Sadfi-Zouaoui Najla, Messaoudi Abdelmonaem
Laboratoire de Mycologie, Pathologies et Biomarqueurs (LR16ES05), Département de Biologie, Université de Tunis-El Manar, Tunis 2092, Tunisia.
Alpha Genomics Private Limited, Islamabad 45710, Pakistan.
Molecules. 2023 Sep 12;28(18):6576. doi: 10.3390/molecules28186576.
Marek's disease virus (MDV) is a highly contagious and persistent virus that causes T-lymphoma in chickens, posing a significant threat to the poultry industry despite the availability of vaccines. The emergence of new virulent strains has further intensified the challenge of designing effective antiviral drugs for MDV. In this study, our main objective was to identify novel antiviral phytochemicals through in silico analysis. We employed Alphafold to construct a three-dimensional (3D) structure of the MDV DNA polymerase, a crucial enzyme involved in viral replication. To ensure the accuracy of the structural model, we validated it using tools available at the SAVES server. Subsequently, a diverse dataset containing thousands of compounds, primarily derived from plant sources, was subjected to molecular docking with the MDV DNA polymerase model, utilizing AutoDock software V 4.2. Through comprehensive analysis of the docking results, we identified Disalicyloyl curcumin as a promising drug candidate that exhibited remarkable binding affinity, with a minimum energy of -12.66 Kcal/mol, specifically targeting the DNA polymerase enzyme. To further assess its potential, we performed molecular dynamics simulations, which confirmed the stability of Disalicyloyl curcumin within the MDV system. Experimental validation of its inhibitory activity in vitro can provide substantial support for its effectiveness. The outcomes of our study hold significant implications for the poultry industry, as the discovery of efficient antiviral phytochemicals against MDV could substantially mitigate the economic losses associated with this devastating disease.
马立克氏病病毒（MDV）是一种高度传染性和持续性的病毒，可导致鸡的T淋巴瘤，尽管有疫苗可用，但仍对家禽业构成重大威胁。新的强毒株的出现进一步加剧了为MDV设计有效抗病毒药物的挑战。在本研究中，我们的主要目标是通过计算机分析鉴定新型抗病毒植物化学物质。我们使用Alphafold构建了MDV DNA聚合酶的三维（3D）结构，该酶是参与病毒复制的关键酶。为确保结构模型的准确性，我们使用SAVES服务器上的工具对其进行了验证。随后，利用AutoDock软件V 4.2，对一个包含数千种主要来源于植物的化合物的多样化数据集与MDV DNA聚合酶模型进行了分子对接。通过对对接结果的综合分析，我们确定二水杨酰姜黄素是一种有前景的候选药物，它表现出显著的结合亲和力，最低能量为-12.66千卡/摩尔，特别靶向DNA聚合酶。为进一步评估其潜力，我们进行了分子动力学模拟，证实了二水杨酰姜黄素在MDV系统中的稳定性。对其体外抑制活性的实验验证可为其有效性提供大量支持。我们的研究结果对家禽业具有重要意义，因为发现针对MDV的高效抗病毒植物化学物质可大幅减轻与这种毁灭性疾病相关的经济损失。
