Abstract:
:We recently described that the chloroxoquinolinic ribonucleoside 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl) quinoline-3-carboxylic acid (compound A) inhibits the human immunodeficiency virus type 1 (HIV-1) enzyme reverse transcriptase (RT), and its replication in primary cells. Based on these findings, we performed kinetic studies to investigate the mode of inhibition of compound A and its aglycan analog (compound B). We found that both molecules inhibited RT activity independently of the template/primer used. Nevertheless, compound A was 10-fold more potent than compound B. Compound A inhibited the RNA-dependent DNA polymerase (RDDP) activity of RT with an uncompetitive and a noncompetitive mode of action with respect to dTTP incorporation and to template/primer (TP) uptake, respectively. The kinetic pattern of the inhibition displayed by compound A was probably due to its greater affinity for the ternary complex (RT-TP-dNTP) than the enzyme alone or the binary complex (RT-TP). Besides, by means of molecular modeling, we show that compound A bound on the NNRTI binding pocket of RT. However, our molecule targets such a site by making novel interactions with the enzyme RT, when compared to NNRTIs. These include a hydrogen bridge between the 2'-OH of our compound and the Tyr675 of the enzyme RT's chain B. Therefore, compound A is able to synergize with both a NRTI (AZT-TP) and a NNRTI (efavirenz). Taken together, our results suggest that compound A displays a novel mechanism of action, which may be different from classical NRTIs and NNRTIs.
journal_name
Curr HIV Resjournal_title
Current HIV researchauthors
Souza TM,Rodrigues DQ,Ferreira VF,Marques IP,da Costa Santos F,Cunha AC,de Souza MC,de Palmer Paixão Frugulhetti IC,Bou-Habib DC,Fontes CFdoi
10.2174/157016209788347958subject
Has Abstractpub_date
2009-05-01 00:00:00pages
327-35issue
3eissn
1570-162Xissn
1873-4251journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Whether HIV-positive injecting drug users (IDUs) are at higher risk of developing drug resistance mutations (DRMs) after methadone maintenance therapy (MMT) than any other HIV-positive population is unclear. OBJECTIVE:To compare the incidence of new DRMs in two population groups: antiretroviraltreatment (AR...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200712173630
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVE:Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. METHOD:Blood samples were o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X16666180219154601
更新日期:2018-01-01 00:00:00
abstract::Hodgkin lymphoma (HL) represents one of the most common types of a non-AIDS-defining tumour that occurs in the HIV population, and its incidence is increasing in the post Highly Active Anti-retroviral Therapy (HAART) era. Despite the aggressiveness of that disease, the outcome of patients with HIV-HL has improved with...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016210790442704
更新日期:2010-03-01 00:00:00
abstract::Over the past 10 years substantial progress has been made in the implementation of prevention of mother-to-child transmission of HIV (PMTCT) interventions in Sub-Saharan Africa (SSA). In spite of this, new pediatric infections remain unacceptably high, contributing the majority (>90%) of the estimated 390,000 infectio...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162x11311020007
更新日期:2013-03-01 00:00:00
abstract:UNLABELLED:Some deficient genetic polymorphisms of the innate immune system have been correlated to a higher susceptibility to different infections, especially in immunocompromised patients. The possible association between an increased incidence of pneumococcal bacteremia in HIV-infected patients, and deficient polymo...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016209787581382
更新日期:2009-03-01 00:00:00
abstract::Objective was to assess dietary intake and physical activity in a Canadian population sample of male patients with HIV and metabolic abnormalities and to compare the data to Canadian recommendations. Sixty-five HIV-infected men with at least one feature associated with the metabolic syndrome (insulin resistance, dysli...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208783571973
更新日期:2008-01-01 00:00:00
abstract::A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely pro...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016207782418470
更新日期:2007-11-01 00:00:00
abstract::Revised Centers for Disease Control and Prevention recommendations on HIV testing now promote testing of most risk groups. However, positive results for low-risk individuals are more likely to be false positives than for high-risk individuals, making clear communication of test results even more imperative. In a study...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x13666150511125629
更新日期:2015-01-01 00:00:00
abstract::Most of the HIV-infected long term survivors show strong CD8+ cell noncytotoxic antiviral response (CNAR) that plays as an important factor for maintaining the relative healthy state of infected individuals. HIV infected former blood donors (FBDs) in Anhui, China are the unique population that considered infected by t...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016209788680561
更新日期:2009-07-01 00:00:00
abstract::Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex bio...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016210791208613
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:The primary objective of this study was to estimate etravirine activity in a cohort of patients infected with non-B subtype HIV-1 and failing nevirapine-based therapy. MATERIALS AND METHODS:Genotypic resistance testing was performed if viral load was >OR= 1,000 copies/ml after receiving at least six months o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016210791111098
更新日期:2010-04-01 00:00:00
abstract::Antiretroviral (ARV) prophylaxis for prevention of mother to child transmission (MTCT) of HIV could affect hemoglobin (Hb) development of infants. A cross-sectional descriptive study was conducted in 24 HIV-infected and 21 HIV-uninfected pregnancies. ARV drugs were administered to HIV-infected pregnancies at 21 weeks ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x12666140713170800
更新日期:2014-01-01 00:00:00
abstract:INTRODUCTION:Tuberculosis (TB) is a pandemic infectious disease especially frequent in HIV-infected patients. Toll-like receptor (TLR) 4 has been described to play a main role in the innate immunity against TB. In fact, single nucleotide polymorphisms (SNPs) in TLRs may influence AIDS disease progression. The associati...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016210791111052
更新日期:2010-04-01 00:00:00
abstract::Modern combination antiretroviral therapy (cART) can bring HIV-1 in blood plasma to level undetectable by standard tests, prevent the onset of acquired immune deficiency syndrome (AIDS), and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, cART is not curative, as within a few weeks of ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666191231105438
更新日期:2020-01-01 00:00:00
abstract::In HIV-1 infected cells, over 40 different mRNA species are produced by alternative splicing of the single HIV-1 primary RNA transcript. In addition, approximately half of the HIV-1 primary RNA transcripts are not spliced and are exported to the cytoplasm where they serve as mRNA and as genomic RNA. In this article, w...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016206775197655
更新日期:2006-01-01 00:00:00
abstract::Most new HIV infections in sub-Saharan Africa now occur in married and cohabiting couples, many of whom do not realize that only one of them may be infected with HIV. HIV-negative individuals living in stable HIV-discordant partnerships (in which one partner is HIV-infected while the other one is not) are twice as lik...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016210793499303
更新日期:2010-09-01 00:00:00
abstract::To promote the initiation of reverse transcription, the HIV-1 virus uses a host tRNA as a primer, tRNA(3Lys). The annealing of tRNA(3Lys) to the viral RNA requires the breaking of the 3D structure of the tRNA and RNA rearrangements, to form a stable initiation complex recognised by the reverse transcriptase. The annea...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162053506919
更新日期:2005-04-01 00:00:00
abstract::One of the major obstacles to effective prolonged CD8 T cell control over HIV and other latent infections may be the intrinsic, genetically programmed barrier to unlimited proliferation that is characteristic of all normal human somatic cells. Replicative senescence, characterized extensively in cell culture for a var...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162033485348
更新日期:2003-04-01 00:00:00
abstract::Premature immunosenescence has been reported in different HIV scenarios. However, how premature is the HIV-related immunosenescent phenotype is still unknown. Thus, the aim of this study was to analyze the immunosenescent status of young viraemic naive HIV-infected individuals, with less than four years from infection...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016211797636008
更新日期:2011-07-01 00:00:00
abstract::Drug use and HIV/AIDS are global public health issues. The World Health Organization (WHO) estimates that up to 30% of HIV infections are related to drug use and associated behaviors. The intersection, of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the health care...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016209788680598
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:China has implemented a nation-wide policy to control mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) since 2011, yet the efficacy of the control policy is less studied. The aim of the present study was to report the data in the prevention of MTCT of HIV in Nantong city, China. ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200810134025
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. OBJECTIVE:In this...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X15666171017122229
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:We studied the clinical presentation, diagnosis, treatment outcome and survival in children with HIV and Tuberculosis (TB) co-infection. METHODS:All HIV infected children with symptoms or signs consistent with tuberculosis were screened. We studied 24 cases of culture confirmed TB from among a cohort of 213...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016207781662434
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade's polymorphisms in its functionally critical regions protease and reverse transcriptase. OBJECTIVE:To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its pare...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200415140652
更新日期:2020-01-01 00:00:00
abstract::Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherenc...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200824104140
更新日期:2020-08-23 00:00:00
abstract:BACKGROUND:A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge. OBJECTIVE:During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162X15666171124122044
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. OBJECTIVE:To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurat...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200720000344
更新日期:2020-01-01 00:00:00
abstract::The development of pre-exposure prophylactics or microbicide products for the reduction or elimination of the sexual transmission of HIV has numerous challenges or barriers to success. Historically traditional dosage forms such as gels have been developed in the field but more recently controlled release dosage forms ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016212799304599
更新日期:2012-01-01 00:00:00
abstract::After the infusion of HIV-1 virus into a host cell, RNA is reverse transcribed to dsDNA, which persists intracellular to the infected cell in a variety of forms. Numerous in-house assays have been developed for the quantification of the different cellular HIV-1 DNA forms; these implement conventional or real-time PCR ...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016209788348001
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:The emergence of drug-resistant viral strains has created the need for the development of novel anti-HIV agents with a diverse structure that targets key enzymes in the HIV lifecycle. OBJECTIVE:Considering the pharmacophore of integrase inhibitors, one of the validated targets for anti-HIV therapy, we desig...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X17666191210105809
更新日期:2020-01-01 00:00:00