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

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3563
Author(s):  
Runjing Wang ◽  
Yinyu Wei ◽  
Meiqin Wang ◽  
Pan Yan ◽  
Hongliang Jiang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zinc Finger ◽  
Binding Mode ◽  
Natural Compounds ◽  
Cd Spectroscopy ◽  
Scientific Basis ◽  
Noncovalent Interaction ◽  
Active Components ◽  
Active Compounds ◽  
Hiv Therapy

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.

scholarly journals Specificity of the HIV-1 Protease on Substrates Representing the Cleavage Site in the Proximal Zinc-Finger of HIV-1 Nucleocapsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér
Keyword(s):  
Amino Acid ◽  
Zinc Finger ◽  
Cleavage Site ◽  
Potential Role ◽  
Binding Mode ◽  
Interaction Energies ◽  
Vitro Assay ◽  
Hiv 1

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.

scholarly journals Mechanism of Compound Houttuynia Mixture as an Anti-COVID-19 Drug Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110167
Author(s):  
Xing-Pan Wu ◽  
Tian-Shun Wang ◽  
Zi-Xin Yuan ◽  
Yan-Fang Yang ◽  
He-Zhen Wu
Keyword(s):  
Molecular Docking ◽  
Target Prediction ◽  
Interaction Network ◽  
Scientific Basis ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Active Components ◽  
Discovery Studio ◽  
The Core ◽  
Pathway Annotation

Objective To explore the anti-COVID-19 active components and mechanism of Compound Houttuynia mixture by using network pharmacology and molecular docking. Methods First, the main chemical components of Compound Houttuynia mixture were obtained by using the TCMSP database and referring to relevant chemical composition literature. The components were screened for OB ≥30% and DL ≥0.18 as the threshold values. Then Swiss Target Prediction database was used to predict the target of the active components and map the targets of COVID-19 obtained through GeneCards database to obtain the gene pool of the potential target of COVID-19 resistance of the active components of Compound Houttuynia mixture. Next, DAVID database was used for GO enrichment and KEGG pathway annotation of targets function. Cytoscape 3.8.0 software was used to construct a “components-targets-pathways” network. Then String database was used to construct a “protein-protein interaction” network. Finally, the core targets, SARS-COV-2 3 Cl, ACE2 and the core active components of Compound Houttuyna Mixture were imported into the Discovery Studio 2016 Client database for molecular docking verification. Results Eighty-two active compounds, including Xylostosidine, Arctiin, ZINC12153652 and ZINC338038, were screened from Compound Houttuyniae mixture. The key targets involved 128 targets, including MAPK1, MAPK3, MAPK8, MAPK14, TP53, TNF, and IL6. The HIF-1 signaling, VEGF signaling, TNF signaling and another 127 signaling pathways associated with COVID-19 were affected ( P < 0.05). From the results of molecular docking, the binding ability between the selected active components and the core targets was strong. Conclusion Through the combination of network pharmacology and molecular docking technology, this study revealed that the therapeutic effect of Compound Houttuynia mixture on COVID-19 was realized through multiple components, multiple targets and multiple pathways, which provided a certain scientific basis of the clinical application of Compound Houttuynia mixture.

Structure Identification and Evaluation of Chemical Components from the Flos Sophorae Immaturus for Inhibitory Effects against HepG2

2021 ◽  
Vol 19 (4) ◽  
pp. 452-457
Author(s):  
Zhaohui Xue ◽  
Weichen Song ◽  
Xin Gao ◽  
Wancong Yu ◽  
Xiaonan Hou ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Scientific Basis ◽  
Added Value ◽  
Structure Identification ◽  
Chemical Components ◽  
Active Components ◽  
Sophora Japonica ◽  
Beneficial Effects ◽  
Cell Proliferation Inhibition ◽  
Inhibition Potency

Flos Sophorae Immaturus, dried buds of Sophora japonica, exhibits multiple pharmacologic activities including anti-inflammatory, antiaging, and antiallergy effects as well as adjunct to standard of care cancer therapy. However, active components responsible for beneficial effects in cancer are not known. In this study, Flos Sophorae Immaturus was obtained by ethanol extraction, and eight components were purified, identified, and tested for HepG2 cell proliferation inhibition potency. The compounds identified to be the most effective inhibitors were campherol > isorhamnetin > quercetin. These data provide theoretical and scientific basis for the further development, utilization, and the promotion of added value of Flos Sophorae Immaturus.

Zinc finger protein ZFP36L1 inhibits flavivirus infection by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways.

2021 ◽  
Author(s):  
Han Chiu ◽  
Hsin-Ping Chiu ◽  
Han-Pang Yu ◽  
Li-Hsiung Lin ◽  
Zih-Ping Chen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Zinc Finger ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Viral Rna ◽  
Rna Decay ◽  
Finger Protein ◽  
Zinc Finger Motifs ◽  
Rna Exosome

Zinc-finger protein 36, CCCH type-like 1 (ZFP36L1), containing tandem CCCH-type zinc-finger motifs with an RNA-binding property, plays an important role in cellular RNA metabolism mainly via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 has potent antiviral activity against influenza A virus infection. However, its role in the host defense response against flaviviruses has not been addressed. Here, we demonstrate that ZFP36L1 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L1 reduced JEV and DENV infection, and ZFP36L1 knockdown enhanced viral replication. ZFP36L1 destabilized the JEV genome by targeting and degrading viral RNA mediated by both 5′-3′ XRN1 and 3′-5′ RNA-exosome RNA decay pathways. Mutation in both zinc-finger motifs of ZFP36L1 disrupted RNA-binding and antiviral activity. Furthermore, the viral RNA sequences specifically recognized by ZFP36L1 were mapped to the 3'-untranslated region of the JEV genome with the AU-rich element (AUUUA) motif. We extend the function of ZFP36L1 to host antiviral defense by directly binding and destabilizing the viral genome via recruiting cellular mRNA decay machineries. Importance Cellular RNA-binding proteins are among the first lines of defense against various viruses, particularly RNA viruses. ZFP36L1 belongs to the CCCH-type zinc-finger protein family and has RNA-binding activity; it has been reported to directly bind to the AU-rich elements (AREs) of a subset of cellular mRNAs and then lead to mRNA decay by recruiting mRNA degrading enzymes. However, the antiviral potential of ZFP36L1 against flaviviruses has not yet been fully demonstrated. Here, we reveal the antiviral potential of human ZFP36L1 against Japanese encephalitis virus (JEV) and dengue virus (DENV). ZFP36L1 specifically targeted the ARE motif within viral RNA and triggered the degradation of viral RNA transcripts via cellular degrading enzymes, 5′-3′ XRN1 and 3′-5′ RNA exosome. These findings provide mechanistic insights into how human ZFP36L1 serves as a host antiviral factor to restrict flavivirus replication.

Inhibition of transcription factor assembly and structural stability on mitoxantrone binding with DNA

2010 ◽  
Vol 30 (5) ◽  
pp. 331-340 ◽  
Author(s):  
Shahper N. Khan ◽  
Mohd Danishuddin ◽  
Asad U. Khan
Keyword(s):  
Transcription Factor ◽  
Binding Mode ◽  
Cd Spectroscopy ◽  
Sequence Specificity ◽  
Mobility Shift ◽  
Dna Complexes ◽  
Naked Dna ◽  
Plasmid Nicking Assay ◽  
Modelling Studies ◽  
Mobility Shift Assay

MTX (mitoxantrone) is perhaps the most promising drug used in the treatment of various malignancies. Comprehensive literature on the therapeutics has indicated it to be the least toxic in its class, although its mechanism of action is still not well defined. In the present study, we have evaluated the associated binding interactions of MTX with naked DNA. The mechanism of MTX binding with DNA was elucidated by steady-state fluorescence and a static-type quenching mechanism is suggested for this interaction. Thermodynamic parameters from van 't Hoff plots showed that the interaction of these drugs with DNA is an entropically driven phenomenon. The binding mode was expounded by attenuance measurements and competitive binding of a known intercalator. Sequence specificity of these drug–DNA complexes was analysed by FTIR (Fourier-transform infrared) spectroscopy and molecular modelling studies. CD spectroscopy and the plasmid nicking assay showed that the binding of this drug with DNA results in structural and conformational perturbations. EMSA (electrophoretic mobility-shift assay) results showed that these drug–DNA complexes prevent the binding of octamer TF (transcription factor) to DNA. In summary, the study implicates MTX-induced conformational instability and transcription inhibition on DNA binding.

Simultaneous Determination of 10-Deacetylbaccatin，Cephalomannine and Taxol in Different Parts of Taxus Media with Different Growth Years by UPLC

2011 ◽  
Vol 108 ◽  
pp. 326-330 ◽  
Author(s):  
Jing Zhang ◽  
Chao Feng Yang ◽  
Ke Yuan
Keyword(s):  
Ultra Performance Liquid Chromatography ◽  
Scientific Basis ◽  
Sichuan Province ◽  
Zhejiang Province ◽  
Taxus Baccata ◽  
Active Components ◽  
Taxus Media ◽  
Hybrid Variety ◽  
Taxus Cuspidate ◽  
Different Parts

Taxus media is the natural hybrid variety of Taxus cuspidate and Taxus baccata, and has been used as an anticancer plant with some medical components-taxanes. In this study, ultra performance liquid chromatography was used for quantification of three major bioactive taxanes in Taxus media, which were collected in Zhejiang province and Sichuan province (China). As a result of this study, a convenient, accurate, rapid and reproducible UPLC method has been developed to successfully quantify 10-Deacetylbaccatin Ⅲ (10-DABⅢ), Cephalomannine and Taxol in the needle and twig of Taxus media. The results indicate that the sequence of the contents of three active components in Taxus media with different parts was needle>twig; the sequence of the contents of three active components in Taxus media with different growth years was 5 year old >4 year old >3 year old; and there were great differences in the contents of three active components in Taxus media between Zhejiang province and Sichuan province. The results also provided a scientific basis for uses of Taxus media.

Synthesis and Antiviral Activity of Dimeric Capsid-Binding Inhibitors of Human Rhinovirus (HRV)

2004 ◽  
Vol 57 (6) ◽  
pp. 553 ◽  
Author(s):  
Guy Y. Krippner ◽  
David K. Chalmers ◽  
Pauline C. Stanislawski ◽  
Simon P. Tucker ◽  
Keith G. Watson
Keyword(s):  
Antiviral Activity ◽  
Human Rhinovirus ◽  
Lower Activity ◽  
Active Compounds ◽  
Low Activity ◽  
Binding Inhibitors

A set of dimeric analogues of known rhinovirus capsid-binders Pleconaril 1 and Pirodavir 55 has been synthesized and tested against two representative human rhinovirus (HRV) strains. Dimers with linker lengths ranging from five atoms up to approximately 60 atoms were prepared by coupling various functionalized monomeric precursors. Many of the dimers showed activity against HRV, with the most active compounds being those with the shorter linking groups. The lower activity of all the dimers relative to similar monomeric compounds, and especially the low activity of the longest dimers, suggests that cooperative bivalent binding is not occurring with any of these compounds.

scholarly journals TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein

2017 ◽  
Vol 91 (9) ◽  
Author(s):  
Xiaojiao Zheng ◽  
Xinlu Wang ◽  
Fan Tu ◽  
Qin Wang ◽  
Zusen Fan ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zinc Finger ◽  
Ebola Virus ◽  
Rna Binding ◽  
E3 Ligase ◽  
Antiviral Protein ◽  
Viral Mrnas ◽  
Target Mrna ◽  
Ubiquitin E3 Ligase ◽  
Target Rna

ABSTRACTZinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAP's activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviral activity of ZAP is regulated.IMPORTANCEZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAP's activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated.

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

2013 ◽  
Vol 23 (17) ◽  
pp. 4911-4918 ◽  
Author(s):  
Venkateshwar Rao Gummadi ◽  
Sujatha Rajagopalan ◽  
Chung-Yeng Looi ◽  
Mohammadjavad Paydar ◽  
Girish Aggunda Renukappa ◽  
...  
Keyword(s):  
Anaplastic Lymphoma Kinase ◽  
Binding Mode ◽  
Wild Type ◽  
Active Compounds ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma

scholarly journals Research Progress on Toxicity of Natural Compounds

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Zhangping Zhou ◽  
Zilong Fu ◽  
Yan Li ◽  
Biao Ren ◽  
Ling Duan ◽  
...  
Keyword(s):  
Natural Resources ◽  
High Efficiency ◽  
Natural Compounds ◽  
Research Progress ◽  
Rational Utilization ◽  
Active Compounds ◽  
Natural Substances ◽  
Low Toxicity ◽  
Further Development ◽  
Active Substances

There are many active substances in natural resources. After years of research, researchers at home and abroad have extracted active compounds and proved that these compounds have low toxicity and high efficiency, but the toxicity of these compounds cannot be ignored. In this paper, the research progress on the toxicity of compounds isolated from various natural substances is reviewed, which provides a reference for the further development and rational utilization of natural compounds.

Sign in / Sign up

Export Citation Format

Share Document