The antiviral lectin cyanovirin-N: probing multivalency and glycan recognition through experimental and computational approaches

2013 ◽  
Vol 41 (5) ◽  
pp. 1170-1176 ◽  
Author(s):  
Brian W. Woodrum ◽  
Jason D. Maxwell ◽  
Ashini Bolia ◽  
S. Banu Ozkan ◽  
Giovanna Ghirlanda
Keyword(s):  
Viral Entry ◽  
High Specificity ◽  
Integrated Approach ◽  
Protein Gp120 ◽  
Computational Work ◽  
Gp120 Glycoprotein ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Envelope Protein Gp120

CVN (cyanovirin-N), a small lectin isolated from cyanobacteria, exemplifies a novel class of anti-HIV agents that act by binding to the highly glycosylated envelope protein gp120 (glycoprotein 120), resulting in inhibition of the crucial viral entry step. In the present review, we summarize recent work in our laboratory and others towards determining the crucial role of multivalency in the antiviral activity, and we discuss features that contribute to the high specificity and affinity for the glycan ligand observed in CVN. An integrated approach that encompasses structural determination, mutagenesis analysis and computational work holds particular promise to clarify aspects of the interactions between CVN and glycans.

Role of P-glycoprotein in the efflux of raltegravir from human intestinal cells and CD4+ T-cells as an interaction target for anti-HIV agents

2013 ◽  
Vol 439 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Yumi Hashiguchi ◽  
Akinobu Hamada ◽  
Takashi Shinohara ◽  
Kiyoto Tsuchiya ◽  
Hirofumi Jono ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intestinal Cells ◽  
P Glycoprotein ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Human Intestinal Cells

The Role of Community Advisory Committees in Clinical Trials of Anti-HIV Agents

1988 ◽  
Vol 10 (4) ◽  
pp. 5 ◽  
Author(s):  
Ronald O. Valdiserri ◽  
Geraldine Maiatico Tama ◽  
Monto Ho
Keyword(s):  
Clinical Trials ◽  
Advisory Committees ◽  
Anti Hiv Agents ◽  
Anti Hiv

scholarly journals New developments in anti-HIV chemotherapy

2001 ◽  
Vol 73 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Erik De Clercq
Keyword(s):  
Reverse Transcriptase ◽  
Viral Entry ◽  
Hiv Infections ◽  
Viral Envelope ◽  
Reverse Transcriptase Inhibitors ◽  
Intact Cells ◽  
Metabolic Characteristics ◽  
Glycoprotein Gp120 ◽  
Anti Hiv Agents ◽  
Anti Hiv

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, tenofovir (PMPA), and disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, and emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir. In addition, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120; (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5; (iii) virus-cell fusion; (iv) viral assembly and disassembly; (v) proviral DNA integration; and (vi) viral mRNA transcription. Also, new NRTIs, NNRTIs, and PIs have been developed that possess respectively improved metabolic characteristics, or increased activity against NNRTI-resistant HIV strains or, as in the case of PIs, a different, nonpeptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells.

Sphingolipids: Modulators of HIV-1 Infection and Pathogenesis

2005 ◽  
Vol 25 (5-6) ◽  
pp. 329-343 ◽  
Author(s):  
Satinder S. Rawat ◽  
Benitra T. Johnson ◽  
Anu Puri
Keyword(s):  
Viral Entry ◽  
Fusion Reaction ◽  
Cell Types ◽  
Host Cells ◽  
Target Membrane ◽  
Cellular Lipids ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Working Hypotheses ◽  
Hiv 1

HIV-1 infects host cells by sequential interactions of its fusion protein (gp120-gp41) with receptors CD4, CXCR4 and/or CCR5 followed by fusion of viral and host membranes. Studies indicate that additional factors such as receptor density and composition of viral and cellular lipids can dramatically modulate the fusion reaction. Lipid rafts, which primarily consist of sphingolipids and cholesterol, have been implicated for infectious route of HIV-1 entry. Plasma membrane Glycosphingolipids (GSLs) have been proposed to support HIV-1 infection in multiple ways: (a) as alternate receptor(s) for CD4-independent entry in neuronal and other cell types, (b) viral transmission, and (c) gp120-gp41-mediated membrane fusion. However, the exact mechanism(s) by which GSLs support fusion is still elusive. This article will focus on the contribution of target membrane sphingolipids and their metabolites in modulating viral entry. We will discuss the current working hypotheses underlying the mechanisms by which these lipids promote and/or block HIV-1 entry. Recent approaches in the design and development of novel glycosyl derivatives, as anti-HIV agents will be summarized.

Сatalytic Phosphorylation of Aromatic C-H Bonds: from Traditional Approaches to Electrochemistry

2019 ◽  
Vol 23 (16) ◽  
pp. 1756-1770
Author(s):  
Sofia Strekalova ◽  
Mikhail Khrizanforov ◽  
Oleg Sinyashin ◽  
Yulia Budnikova
Keyword(s):  
Organophosphorus Compounds ◽  
Normal Pressure ◽  
Acid Group ◽  
Synthetic Methods ◽  
Heteroaromatic Compounds ◽  
Anti Cancer ◽  
Phosphonic Acid Group ◽  
Traditional Approaches ◽  
Anti Hiv Agents ◽  
Anti Hiv

The interest in organophosphorus compounds with a C-P bond is due to their wide use in various fields, especially in medicine and agrochemistry. Prominent examples of anti-cancer, antibacterial, and anti-HIV agents are therapeutic candidates containing a phosphonic acid group fragment. This review provides modern synthetic methods for obtaining phosphorylated aromatic and heteroaromatic compounds with the participation of complexes and salts of various metals developed in recent years as well modern protocol - electrochemical synthesis which allows carrying out reactions at room temperature and normal pressure with no additional oxidants or bases. Herein, we demonstrate new trends and evolution of phosphorylation reactions in catalysis.

Marine Natural Products as Lead Anti-HIV Agents

2003 ◽  
Vol 3 (5) ◽  
pp. 401-424 ◽  
Author(s):  
D. Gochfeld ◽  
K. El Sayed ◽  
M. Yousaf ◽  
J. Hu ◽  
P. Bartyzel ◽  
...  
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Anti Hiv Agents ◽  
Anti Hiv

Rational Design of Colchicine Derivatives as anti-HIV Agents via QSAR and Molecular Docking

2019 ◽  
Vol 15 (4) ◽  
pp. 328-340 ◽  
Author(s):  
Apilak Worachartcheewan ◽  
Napat Songtawee ◽  
Suphakit Siriwong ◽  
Supaluk Prachayasittikul ◽  
Chanin Nantasenamat ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rational Design ◽  
External Validation ◽  
Rational Drug Design ◽  
Support Vector ◽  
Data Set ◽  
Qsar Models ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Colchicine Derivatives

Background: Human immunodeficiency virus (HIV) is an infective agent that causes an acquired immunodeficiency syndrome (AIDS). Therefore, the rational design of inhibitors for preventing the progression of the disease is required. Objective: This study aims to construct quantitative structure-activity relationship (QSAR) models, molecular docking and newly rational design of colchicine and derivatives with anti-HIV activity. Methods: A data set of 24 colchicine and derivatives with anti-HIV activity were employed to develop the QSAR models using machine learning methods (e.g. multiple linear regression (MLR), artificial neural network (ANN) and support vector machine (SVM)), and to study a molecular docking. Results: The significant descriptors relating to the anti-HIV activity included JGI2, Mor24u, Gm and R8p+ descriptors. The predictive performance of the models gave acceptable statistical qualities as observed by correlation coefficient (Q2) and root mean square error (RMSE) of leave-one out cross-validation (LOO-CV) and external sets. Particularly, the ANN method outperformed MLR and SVM methods that displayed LOO−CV 2 Q and RMSELOO-CV of 0.7548 and 0.5735 for LOOCV set, and Ext 2 Q of 0.8553 and RMSEExt of 0.6999 for external validation. In addition, the molecular docking of virus-entry molecule (gp120 envelope glycoprotein) revealed the key interacting residues of the protein (cellular receptor, CD4) and the site-moiety preferences of colchicine derivatives as HIV entry inhibitors for binding to HIV structure. Furthermore, newly rational design of colchicine derivatives using informative QSAR and molecular docking was proposed. Conclusion: These findings serve as a guideline for the rational drug design as well as potential development of novel anti-HIV agents.

Modeling Anti-HIV Compounds: The Role of Analogue-Based Approaches

2012 ◽  
Vol 8 (3) ◽  
pp. 224-248 ◽  
Author(s):  
Hemant Kumar Srivastava ◽  
Mohammed H. Bohari ◽  
G. Narahari Sastry
Keyword(s):  
Anti Hiv
Sign in / Sign up

Export Citation Format

Share Document