Interaction of Natural Compounds in Licorice and Turmeric with HIV-NCp7 Zinc Finger Domain: Potential Relevance to the Mechanism of Antiviral Activity

Abstract

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.

Interaction between Curcumin and β-Casein: Multi-Spectroscopic and Molecular Dynamics Simulation Methods

“…Zhang et al [ 10 ] found that hydrophobic interaction and hydrogen bond promoted the myosin-curcumin complex by MD simulation, and they found that the quenching mechanism of curcumin on myosin was static quenching by spectral experiment, which was beneficial to the formation of myosin−curcumin complex. Wang et al [ 12 ] found that there was face-to-face π-π stacking between the tryptophan of nucleocapsid proteins and the aromatic rings of curcumin.…”

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

“…Further recently a study demonstrated effects of crude extracts of G. glabra along with other plant extract against IAV titer (P ≤ 0.05) ( Mehrbod et al, 2021 ). Similarly, a very recent study demonstrated noncovalent binding interaction of isoliquiritin (an isolate of G. glabra ) with HIV-NCp7 (C-terminal zinc finger) ( Wang et al, 2021 ).…”

Curcumae Rhizoma: A botanical drug against infectious diseases

“…Recent studies show that curcumin inhibits trans-activator of transcription protein transactivation of the HIV1-LTR genome, inflammatory molecules (interleukins, TNF-α, NF-κB, COX-2) and various HIV associated kinases including tyrosine kinase, PAK1, MAPK, and PKC ( Prasad and Tyagi, 2015 ). In addition, Curcumae Rhizoma inhibits nucleocapsid proteins which play a key role in controlling HIV viral replication ( Wang et al, 2021 ).…”