Fatriansyah Jaka Fajar, Rizqillah Raihan Kenji, Yandi Muhammad Yusup
Department of Metallurgical and Materials Engineering, Faculty of Engineering, University of Indonesia, Depok 16424, Jawa Barat, Indonesia.
J Trop Med. 2022 Mar 20;2022:7254990. doi: 10.1155/2022/7254990. eCollection 2022.
Dengue fever is a disease spread by the DENV virus through mosquitoes. This disease is dangerous because there is no specific drug, vaccine, or antiviral against the DENV virus, insisting on drug discovery for dengue fever. RNA-dependent RNA polymerase (RdRp) enzyme in DENV can be a drug target because it has an important role in the virus replication process. In this research, in silico simulations were carried out on bioflavonoid compounds, namely, Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin with Quercetin as control ligand. QSAR analysis showed that all ligand has the probability to be antiviral and RNA synthesis inhibitor. Docking scores showed that Myricetin, Hesperidin, and Fisetin show strong performance while Hesperidin, Hesperetin, and Naringenin showed strong performance in MM/GBSA. Only Hesperidin showed strong performance in both scorings. Further investigation by ADMET analysis was done to investigate toxicology and pharmacological properties. Our molecular dynamics study through RMSD showed that even though Quercetin does not give good scoring values in both docking score and MM/GBSA, it has robust stable interaction to RdRp. The strong performance of Hesperidin was also validated by protein-ligand contact fraction in 5 ns. Overall, we observed that Hesperidin shows good potential as a DENV-3-RdRp inhibitor in par with Quercetin, although further in vitro study should be conducted.
登革热是一种由登革病毒通过蚊子传播的疾病。这种疾病很危险，因为没有针对登革病毒的特效药物、疫苗或抗病毒药物，因此坚持进行登革热药物研发。登革病毒中的RNA依赖性RNA聚合酶（RdRp）酶可成为药物靶点，因为它在病毒复制过程中起着重要作用。在本研究中，对生物类黄酮化合物，即非瑟酮、高良姜素、橙皮素、橙皮苷、杨梅素和柚皮素进行了计算机模拟，以槲皮素作为对照配体。定量构效关系（QSAR）分析表明，所有配体都有成为抗病毒和RNA合成抑制剂的可能性。对接分数显示，杨梅素、橙皮苷和非瑟酮表现出较强的性能，而橙皮苷、橙皮素和柚皮素在MM/GBSA中表现出较强的性能。只有橙皮苷在两种评分中都表现出较强的性能。通过ADMET分析进行了进一步研究，以考察其毒理学和药理学特性。我们通过均方根偏差（RMSD）进行的分子动力学研究表明，尽管槲皮素在对接分数和MM/GBSA中都没有给出良好的评分值，但它与RdRp具有稳健稳定的相互作用。橙皮苷的强性能也通过5纳秒内的蛋白质-配体接触分数得到了验证。总体而言，我们观察到，橙皮苷作为登革病毒3型RdRp抑制剂具有与槲皮素相当的良好潜力，不过还应进行进一步的体外研究。
