Screening of Potential HIV-1 Inhibitors/ Replication Blockers Using Secure Lentiviral in Vitro System (original) (raw)
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Antiviral Research, 2009
Please cite this article in press as: Garcia, J.-M., et al., High-throughput screening using pseudotyped lentiviral particles: A strategy for the identification of HIV-1 inhibitors in a cell-based assay. a b s t r a c t Two decades after its discovery the human immunodeficiency virus (HIV) is still spreading worldwide and killing millions. There are 25 drugs formally approved for HIV currently on the market, but side effects as well as the emergence of HIV strains showing single or multiple resistances to current drugtherapy are causes for concern. Furthermore, these drugs target only 4 steps of the viral cycle, hence the urgent need for new drugs and also new targets. In order to tackle this problem, we have devised a cell-based assay using lentiviral particles to look for post-entry inhibitors of HIV-1. We report here the assay development, validation as well as confirmation of the hits using both wild-type and drug-resistant HIV-1 viruses. The screening was performed on an original library, rich in natural compounds and pure molecules from Traditional Chinese Medicine pharmacopoeia, which had never been screened for anti-HIV activity. The identified hits belong to four chemical sub-families that appear to be all non-nucleoside reverse transcriptase inhibitors (NNRTIs). Secondary tests with live viruses showed that there was good agreement with pseudotyped particles, confirming the validity of this approach for high-throughput drug screens. This assay will be a useful tool that can be easily adapted to screen for inhibitors of viral entry.
Antimicrobial Agents and Chemotherapy, 2003
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Novel targets for the management of HIV infection have become increasingly relevant in view of extensive drug resistance, side effects and high pill burden of some of the conventional anti-retroviral agents. These agents include chemokine receptor antagonists and the integrase inhibitors which were recently approved for HIV treatment, as well as numerous other agents directed to previously untested targets such as the maturation inhibitors, pharmacological CDK inhibitors, TateTAR interaction inhibitors, anti-CD4 monoclonal antibody, antisense oligonucleotides, Use of new agents with novel mechanism of action requires the development of new laboratory assays to detect viral tropism and new resistance mutations. This review discusses issues surrounding the development of these new agents as well as various traditional approaches for the treatment of AIDS.
EASY-HIT: HIV Full-Replication Technology for Broad Discovery of Multiple Classes of HIV Inhibitors
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Antiretroviral Drugs Development; Past, Present and Future
Thirty years after the discovery of human immunodeficiency virus (HIV), more than 29 antiretroviral have been introduced. HIV at present can be managed though; it comes with consequences such as toxicity due to long term use of antiretroviral, development of resistance by HIV-1 strains and other viral or bacterial infections associated with it. Issues such as latency, socioeconomic problem in the developing world has been of considerable concern. The benefits of highly active antiretroviral therapy (HAART) in the developed countries far outweighed those in the underdeveloped nations. HIV belongs to the genus Lentivirus and family Retroviridae, possess a diploid RNA and a cone shaped capsid core particles. The virus consists of major and minor structural and nonstructural proteins that perform different roles in the virus life cycle. In this review we seek to give a comprehensive account of the past, present and future directions in the development of antiretroviral drug. There are five classes of antiretroviral inhibitors which target HIV-1's reverse transcriptase, protease, integrase, envelope fusion and co-receptor binding thereby disrupting virus replicative cycle. Strategies have emerged on how to better manage HIV Review Article