Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Ningxia Pharmaceutical Inspection and Research Institute, Yinchuan 750001, China.
Molecules. 2021 Jun 10;26(12):3563. doi: 10.3390/molecules26123563.
Nucleocapsid proteins (NCp) are zinc finger (ZF) proteins, and they play a central role in HIV virus replication, mainly by interacting with nucleic acids. Therefore, they are potential targets for anti-HIV therapy. Natural products have been shown to be able to inhibit HIV, such as turmeric and licorice, which is widely used in traditional Chinese medicine. Liquiritin (LQ), isoliquiritin (ILQ), glycyrrhizic acid (GL), glycyrrhetinic acid (GA) and curcumin (CUR), which were the major active components, were herein chosen to study their interactions with HIV-NCp7 C-terminal zinc finger, aiming to find the potential active compounds and reveal the mechanism involved. The stacking interaction between NCp7 tryptophan and natural compounds was evaluated by fluorescence. To elucidate the binding mode, mass spectrometry was used to characterize the reaction mixture between zinc finger proteins and active compounds. Subsequently, circular dichroism (CD) spectroscopy and molecular docking were used to validate and reveal the binding mode from a structural perspective. The results showed that ILQ has the strongest binding ability among the tested compounds, followed by curcumin, and the interaction between ILQ and the NCp7 zinc finger peptide was mediated by a noncovalent interaction. This study provided a scientific basis for the antiviral activity of turmeric and licorice.
核衣壳蛋白(NCp)是锌指(ZF)蛋白,它们在 HIV 病毒复制中起核心作用,主要通过与核酸相互作用。因此,它们是抗 HIV 治疗的潜在靶点。天然产物已被证明能够抑制 HIV,如姜黄和甘草,甘草在中药中广泛使用。甘草素(LQ)、异甘草素(ILQ)、甘草酸(GL)、甘草次酸(GA)和姜黄素(CUR)是其主要的活性成分,选择它们来研究它们与 HIV-NCp7 C 末端锌指的相互作用,旨在寻找潜在的活性化合物并揭示相关机制。通过荧光评估 NCp7 色氨酸与天然化合物之间的堆积相互作用。为了阐明结合模式,使用质谱法来表征锌指蛋白与活性化合物之间的反应混合物。随后,圆二色性(CD)光谱和分子对接用于从结构角度验证和揭示结合模式。结果表明,在测试的化合物中,异甘草素的结合能力最强,其次是姜黄素,异甘草素与 NCp7 锌指肽之间的相互作用是通过非共价相互作用介导的。这项研究为姜黄和甘草的抗病毒活性提供了科学依据。