Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation.

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world's most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes.

Design, synthesis and evaluation of cytotoxic, antimicrobial, and anti-HIV-1 activities of new 1,2,3,4-tetrahydropyrimidine derivatives.

A series of new 1,2,3,4-tetrahydropyrimidine (THPM) derivatives were designed and synthesized within a one-pot three component Biginelli reaction. The structures of compounds were characterized by FT-IR, 1HNMR, mass spectroscopy, and elemental analysis. All synthesized derivatives were screened for their cytotoxic, antimicrobial, and anti-HIV activities.

In vitro effect of branched polyethyleneimine (bPEI) on cells infected with human immunodeficiency virus: enhancement of viral replication.

Polyethyleneimine (PEI) is a chemical compound that used is as a carrier in gene therapy/delivery. Some studies have investigated the microbicidal potential and antiviral activity (prophylactic or therapeutic) of PEI and its derivatives. The aim of this study was to investigate the effect of branched polyethyleneimine (bPEI) on human immunodeficiency virus (HIV) replication.

Design, Synthesis, Docking Studies and Biological Activities Novel 2,3- Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents.

Background: Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential.

Objective: To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity.

Novel Benzoxazin-3-one Derivatives: Design, Synthesis, Molecular Modeling, Anti-HIV-1 and Integrase Inhibitory Assay.

Introduction: Integrase is a validated drug target for anti-HIV-1 therapy. The second generation integrase inhibitors display π-stacking interaction ability with 3'-end nucleotide as a streamlined metal chelating pharmacophore.

Methods: In this study, we introduced benzoxazin-3-one scaffold for integrase inhibitory potential as bioisostere replacement strategy of 2-benzoxazolinone.

Anti-viral Effects of Superpositively Charged Mutant of Green Fluorescent Protein.

Background: Supercharged GFP proteins were known as effective carriers for delivery of macromolecules into eukaryotic cells as well as fluorescent fusion tags for in vitro and in vivo detection.

Objective: Herein, anti-viral effects of +36 GFP and its anti-tumor effects were studied in vitro and in vivo, respectively.

Methods: We evaluated anti-HIV, anti-HSV, and anti-HCV effects of +36 GFP in vitro using ELISA, and real time PCR as common techniques for their detection, respectively.

In Vitro Anti-Viral Effects of Small Heat Shock Proteins 20 and 27: A Novel Therapeutic Approach.

Background: The protective effects of heat shock proteins (Hsps) were studied in some infectious and non-infectious diseases, but their specificity was slightly known in various disorders. Among Hsps, small Hsps (e.g.

Synthesis, Molecular Modelling and Biological Studies of 3-hydroxypyrane- 4-one and 3-hydroxy-pyridine-4-one Derivatives as HIV-1 Integrase Inhibitors.

Background: Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against HIV, for avoiding the drug resistance issue.

Objective: To develop novel HIV-1 IN inhibitors, a series of 3-hydroxy-pyrane-4-one (HP) and 3- hydroxy-pyridine-4-one (HPO) derivatives have been rationally designed and synthesized.

Methods: To provide a significant characterization of the novel compounds, in-depth computational analysis was performed using a novel HIV-1 IN/DNA binary 3D-model for investigating the binding mode of the newly conceived molecules in complex with IN.

Inherent anti-HIV activity of biocompatible anionic citrate-PEG-citrate dendrimer.

The development of new combinations to empower better protection against HIV infection is particularly important. Anionic polymers can block HIV infection. In the current study, first generation (G1) and second generation (G2) novel water-soluble anionic citrate-PEG-citrate dendrimers were synthesized and characterized with Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and dynamic light scattering (DLS) methods.

Design, Synthesis, and Anti-HIV-1 Evaluation of a Novel Series of 1,2,3,4-Tetrahydropyrimidine-5-Carboxylic Acid Derivatives.

A series of tetrahydropyrimidine derivatives (2a - 2l) were designed, synthesized, and screened for anti-HIV-1 properties based on the structures of HIV-1 gp41 binding site inhibitors, NB-2 and NB-64. A computational study was performed to predict the pharmacodynamics, pharmacokinetics, and drug-likeness features of the studied molecules. Docking studies revealed that the carboxylic acid group in the molecules forms salt bridges with either Lys574 or Arg579.

Design, Synthesis, Molecular Modeling, ADME Studies and Anti-HIV-1 Assay of New Diazocoumarin Derivatives.

Some new diazo incorporated coumarin compounds were designed and synthesized to evaluate their anti-HIV activity. Overall, compounds were active against HIV at 100 μM. Additionally, no cytotoxic effect was observed at this concentration.

Antiviral Effects of Saffron and its Major Ingredients.

Background: The lack of an effective vaccine against viral infections, toxicity of the synthetic anti-viral drugs and the generation of resistant viral strains led to discover novel inhibitors. Recently, saffron and its compounds were used to treat different pathological conditions.

Method: In this study, we tested the anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major ingredients including crocin and picrocrocin as well as cytotoxicity in vitro.

Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 4-[4-Arylpyridin-1(4H)-yl]benzoic Acid Derivatives as Anti-HIV-1 Agents.

The structural similarities between N1 substituted 1,4-dihydropyridines and the known gp41 inhibitors, NB-2 and NB-64, were considered in the current research for the design of some novel anti-HIV-1 agents. A series of novel 4-[4-arylpyridin-1(4H)-yl]benzoic acid derivatives were synthesized and after a comprehensive structural elucidation were screened for in vitro anti-HIV-1 activity. Most of the tested compounds displayed moderate to good inhibitory activity against HIV-1 growth and were evaluated for in vitro cytotoxic activity using XTT assay at the concentration of 100 μm.

Trimethyl Chitosan Improves Anti-HIV Effects of Atripla as a New Nanoformulated Drug.

Background: Highly active antiretroviral therapy (HAART) has been commonly used for HIV treatment. Its main drawbacks like drug resistance and side effects raised researcher's interest to find new approaches for its treatment. Trimethyl chitosan is one of the drug carriers which has been introduced recently.

Venom Components of Iranian Scorpion Hemiscorpius lepturus Inhibit the Growth and Replication of Human Immunodeficiency Virus 1 (HIV-1).

Background: During the recent years, significant progress has been achieved on development of novel anti-viral drugs. Natural products are assumed as the potential sources of novel anti-viral drugs; therefore, there are some previous studies reporting the anti-viral compounds from venomous animals. Based on the significant value for tracing of non-toxic anti-viral agents from natural resources, this study was aimed to investigate the anti-viral activity of some HPLC purified fractions derived from the venom of Iranian scorpion, Hemiscorpius lepturus, against human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1).

Impact of TGF-β1 Gene Polymorphism (rs1800469) on Treatment Response to Pegylated Interferon/Ribavirin in Iranian Patients with Hepatitis C.

Background: Hepatitis C virus as a major cause of chronic liver disease affects more than 170 million people worldwide. Recent studies have claimed that single nucleotide polymorphisms (SNPs) for the transforming growth factor-β1 (TGF-β1) gene were strongly associated with the antiviral treatment response. Thus, the present study aimed at the determination of distribution of the rs1800469 (C/T) polymorphism among Iranian with chronic hepatitis C.

Toward the development of a single-round infection assay based on EGFP reporting for anti-HIV-1 drug discovery.

Background: The rapid increase of HIV-1 strains resistant to current antiretroviral drugs is a challenge for successful AIDS therapy. This necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro drug discovery is a priority. Herein, we report the modification of a previously developed system for increased sensitivity, ease of use, and cost-efficiency, based on the application of the EGFP marker.

Inhibitory Activity of Avicennia marina, a Medicinal Plant in Persian Folk Medicine, against HIV and HSV.

Avicennia marina (Avicenniaceae) is a species of mangrove tree used for treatment of small pox lesions in Persian folk medicine. The antiviral activity of methanol, ethanol, water, chloroform and n-hexane extracts was evaluated against HIV-1 and HSV. Methanol extract had the highest antiviral activity and the most polar fraction of this extract (fraction D) inhibited HSV with TI and SI values of 57.

Lamivudine-PEGylated chitosan: a novel effective nanosized antiretroviral agent.

Due to the fact that a definite treatment for AIDS disease has not been discovered so far, antiretroviral drugs are relatively significant in controlling the disease. In this study, Lamivudine- which is an old and effective anti-AIDS drug- was connected to PEGylated chitosan nanoparticle in order to produce a new and greater version of Lamivudine. First, physicochemical studies such as HNMR, FTIR spectroscopy and CHN analysis were performed to ensure the proper synthesis.

Design of Small Molecules with HIV Fusion Inhibitory Property Based on Gp41 Interaction Assay.

Background: Gp41 of HIV (Human Immunodeficiency Virus) is a protein that mediates fusion between viral and cellular membranes. The agent, T-20, which has been approved for HIV inhibition, can restrain Gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day.

Methods: Several molecules like NB-2 and NB-64 have been discovered that can inhibit HIV infection.

Inhibition of HIV and HSV infection by vaginal lactobacilli in vitro and in vivo.

Background And The Purpose Of The Study: The cervico-vaginal mucosa which is populated with microflora (mostly includes lactobacilli) is the portal of entry for sexually transmitted pathogens.

Methods: The in vitro anti-viral effect of vaginal and non-vaginal lactobacillus was evaluated using single cycle HIV-1 replication and HSV-2 plaque reduction assays. The XTT proliferation assay was used to monitor the cellular toxicity.

The in vitro anti-viral potential of Setarud (IMOD™), a commercial herbal medicine with protective activity against acquired immune deficiency syndrome in clinical trials.

Objectives: Setarud (IMOD™) is a herbal medicine with beneficial effect for patients suffering Human immunodeficiency virus (HIV) infection and has been approved for IV (intra venues) injection. The beneficial effect of IMOD administration for acquired immune deficiency syndrome (AIDS) patient has been proved in previous clinical trials. Here the in vitro inhibitory effect of IMOD against HIV-1, Herpes simplex virus (HSV) and murine leukemia viruses (MLV) was evaluated.

Introducing a frameshift mutation to the POL sequence of HIV-1 provirus and evaluation of the immunogenic characteristics of the mutated virions (RINNL4-3).

Inactivation of the reverse transcriptase (RT) and integrase (IN) enzymes can abolish the replication of the human immunodeficiency virus (HIV) and, thus, its infectivity. Here, inactivated HIV particles convenient for designing virus-like particle (VLP) based vaccines have been produced. Inactivated HIV-provirus was created by introducing a frame shift mutation.

Application of outer membrane vesicle of Neisseria meningitidis serogroup B as a new adjuvant to induce strongly Th1-oriented responses against HIV-1.

Despite the worldwide efforts made in the field of HIV vaccine development, an efficient AIDS vaccine strategy is still vague. Virus-like particles (VLPs) are one of the introduced aspects for HIV vaccine development since the non-replicative nature of HIV VLPs, resulting from the lack of viral genomic RNA, makes them suitable for broad applications. We have previously designed and introduced non-infectious VLPs (mzNL4-3) by introduction of a deletion mutation in the reverse transcriptase and integrase coding regions of HV-1.

Application of SCR priming VLP boosting as a novel vaccination strategy against HIV-1.

Human immunodeficiency virus infection is a worldwide health problem and a protective vaccine is desperately needed to control the AIDS pandemics. To address this concern, we previously constructed single-cycle replicable (SCR) HIV-1 virions, which completely maintained the antigenic structures of HIV-1. Herein, to optimize a vaccination strategy, we studied the immunogenicity of produced SCR virions and adjuvant-formulated HIV-1 virus-like particles (VLPs) in homologous and heterologous prime-boosting regimens.