Abstract:
:The introduction of potent combination therapies in the mid-90s had a tremendous effect on AIDS mortality. However, drug resistance has been a major factor contributing to antiretroviral therapy failure. Currently, there are 26 drugs approved for treating human immunodeficiency virus (HIV) infections, although some of them are no longer prescribed. Most of the available antiretroviral drugs target HIV genome replication (i.e. reverse transcriptase inhibitors) and viral maturation (i.e. viral protease inhibitors). Other drugs in clinical use include a viral coreceptor antagonist (maraviroc), a fusion inhibitor (enfuvirtide) and two viral integrase inhibitors (raltegravir and elvitegravir). Elvitegravir and the nonnucleoside reverse transcriptase inhibitor rilpivirine have been the most recent additions to the antiretroviral drug armamentarium. An overview of the molecular mechanisms involved in antiretroviral drug resistance and the role of drug resistance-associated mutations was previously presented (Menéndez-Arias, L., 2010. Molecular basis of human immunodeficiency virus drug resistance: an update. Antiviral Res. 85, 210-231). This article provides now an updated review that covers currently approved drugs, new experimental agents (e.g. neutralizing antibodies) and selected drugs in preclinical or early clinical development (e.g. experimental integrase inhibitors). Special attention is dedicated to recent research on resistance to reverse transcriptase and integrase inhibitors. In addition, recently discovered interactions between HIV and host proteins and novel strategies to block HIV assembly or viral entry emerge as promising alternatives for the development of effective antiretroviral treatments.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Menéndez-Arias Ldoi
10.1016/j.antiviral.2013.01.007subject
Has Abstractpub_date
2013-04-01 00:00:00pages
93-120issue
1eissn
0166-3542issn
1872-9096pii
S0166-3542(13)00022-3journal_volume
98pub_type
杂志文章,评审abstract::Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.04.003
更新日期:2016-07-01 00:00:00
abstract::The aminoadamantanes, amantadine and rimantadine, have been used to prevent and treat influenza A virus infections for many years. Several reports have shown an increased level of resistance to these drugs, particularly among influenza A(H3N2) subtype viruses, during recent years. We observed an increase in amantadine...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2010.08.013
更新日期:2010-11-01 00:00:00
abstract::Because encapsulation of antiviral drugs in liposomes resulted generally in improved activity against retroviral replication in vivo, the antiviral effects of free-SPC3 and liposome-associated SPC3 were compared in cultured human lymphocytes infected with HIV-1. SPC3 was entrapped in various liposomal formulations, ei...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(02)00002-5
更新日期:2002-06-01 00:00:00
abstract::The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is an essential component of the replication/transcription complex. It comprises various domains, the organization of which differs between CoV genera, d...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2017.11.001
更新日期:2018-01-01 00:00:00
abstract::Human papilloma virus (HPV)-16 is the prevalent genotype associated with cervical tumours. Virus-like-particle (VLP)-based vaccines have proven to be effective in limiting new infections of high-risk HPVs, but their high cost has hampered their use, especially in the poor developing countries. Avipox-based recombinant...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2015.01.012
更新日期:2015-04-01 00:00:00
abstract::Current therapies for chronic hepatitis B virus infection (CHB) - nucleos(t)ide analogue reverse transcriptase inhibitors and interferons - result in low rates of functional cure defined as sustained off-therapy seroclearance of hepatitis B surface antigen (HBsAg). One likely reason is the inability of these therapies...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2015.06.019
更新日期:2015-09-01 00:00:00
abstract::The family Flaviviridae comprises several major human pathogens including hepatitis C virus (genus hepacivirus), yellow fever virus, West Nile virus and dengue virus (genus flavivirus). Flaviviridae genomes comprise a single-stranded RNA segment encoding a single polyprotein that is subsequently processed into 10 matu...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2014.02.006
更新日期:2014-05-01 00:00:00
abstract::Site-directed in vitro mutagenesis was used to create analogs of human interferons (IFNs)-alpha 1 and -alpha 4. Analogs were expressed in vitro using SP6 RNA polymerase and a rabbit reticulocyte lysate cell-free protein synthesis system. Amino acid substitutions for the highly conserved residues at positions 33, 121, ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(89)90066-1
更新日期:1989-08-01 00:00:00
abstract::Chikungunya virus (CHIKV) is an arthropod-borne alphavirus. Alphaviruses are positive strand RNA viruses that require a 5' cap structure to direct translation of the viral polyprotein and prevent degradation of the viral RNA genome by host cell nucleases. Formation of the 5' RNA cap is orchestrated by the viral protei...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2018.03.013
更新日期:2018-06-01 00:00:00
abstract::Dengue virus (DENV) infection is one of the most important infectious diseases in tropical and subtropical regions around the world. Previously, we performed an initial phenotypic screening of 7000 compounds using DENV type 2 (DENV2)-infected BHK-21 cells to identify small molecules which could inhibit virus replicati...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2020.104969
更新日期:2020-12-01 00:00:00
abstract::Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the stable genomic form as the template for viral transcription, plays a crucial role in viral persistence which remains a major global health problem. While accumulating evidence suggests the involvement of transcription factors and epigenetic machinery...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2018.03.008
更新日期:2018-05-01 00:00:00
abstract::This review describes the procedures for the use of fluorochrome labeled monoclonal antibodies and flow cytometry for the detection and quantification of virus infected cells. The application of this technology for (1) identifying virus infected cells in clinical specimens obtained from human cytomegalovirus (HCMV) an...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/s0166-3542(99)00039-x
更新日期:1999-08-01 00:00:00
abstract::In Western countries, chronic hepatitis C virus (HCV)-infection mostly affects former and active substance users. The effect of active substance use on interferon (IFN)-responsiveness and therapy efficacy is not well understood. In this study, we compared natural killer (NK) cell activity and function in healthy contr...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2012.12.025
更新日期:2013-03-01 00:00:00
abstract::This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2018.04.017
更新日期:2018-07-01 00:00:00
abstract::Herpes simplex virus-1 (HSV-1) infection is known to cause skin blisters, keratitis as well as deadly cases of encephalitis in some situations. Only a few therapeutic modalities are available for this globally prevalent infection. Very recently, a small molecule BX795 was identified as an inhibitor of HSV-1 protein sy...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2020.104814
更新日期:2020-08-01 00:00:00
abstract::In this study we tested whether HIV-1 replication could be inhibited by stable RNAi-mediated knockdown of cellular co-factors. Cell lines capable of expressing shRNAs against 30 candidate co-factors implicated at different steps of the viral replication cycle were generated and analyzed for effects on cell viability a...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2010.11.005
更新日期:2011-01-01 00:00:00
abstract::Treatment of the chronic hepatitis C virus (HCV) infection is an unmet medical need, and the HCV NS3 serine protease (NS3-SP) has been used as an attractive target of antiviral screening against HCV. To find naturally chemical entities as lead compounds from which novel anti-HCV agents could be developed, bioassay-gui...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2007.06.001
更新日期:2007-10-01 00:00:00
abstract::Coxsackievirus B3 (CVB3) is a common pathogen of myocarditis. We previously synthesized a siRNA targeting the CVB3 protease 2A (siRNA/2A) gene and achieved reduction of CVB3 replication by 92% in vitro. However, like other drugs under development, CVB3 siRNA faces a major challenge of targeted delivery. In this study,...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2009.07.005
更新日期:2009-09-01 00:00:00
abstract::HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(99)00014-5
更新日期:1999-07-01 00:00:00
abstract::The outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience o...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2013.08.016
更新日期:2013-11-01 00:00:00
abstract::The prevention and control of disease caused by seasonal and potential pandemic influenza viruses is currently managed by the use influenza vaccines and antivirals. The adamantanes (amantadine and rimantadine) were the first antivirals licensed for use against influenza A viruses and have been used extensively in some...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2006.08.002
更新日期:2007-02-01 00:00:00
abstract::The TC-83 vaccine strain of Venezuelan equine encephalitis virus (VEEV) causes encephalitis and death in C3H/HeN mice infected by intranasal (i.n.) instillation. Since TC-83 is exempt as a select agent, this mouse model was used in the evaluation of antiviral therapies. Virus titers in the brains of infected mice peak...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2008.01.007
更新日期:2008-06-01 00:00:00
abstract::The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2011.08.016
更新日期:2011-11-01 00:00:00
abstract::Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccine...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2008.08.002
更新日期:2008-12-01 00:00:00
abstract::The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to d...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2017.07.016
更新日期:2017-09-01 00:00:00
abstract::Favipiravir (T-705) is a broad spectrum antiviral which has been approved in Japan for the treatment of severe influenza virus infections. We reported earlier that favipiravir inhibits the in vitro replication of CHIKV and protects against disease progression in CHIKV-infected immunodeficient mice. We here explored wh...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2017.09.016
更新日期:2018-01-01 00:00:00
abstract::The present study was undertaken to examine the potential of rectal route of immunization for induction of protective immunity in the female genital tract against genital herpes infection in mice. A single rectal immunization of female C57Bl/6 mice with live attenuated herpes simplex virus type 2 lacking thymidine kin...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2007.12.014
更新日期:2008-06-01 00:00:00
abstract::Almost 30 years ago it was proposed that the selection for antiviral drug resistance should be used as an indicator of antiviral drug activity. In addition to discriminating between cellular toxicity and specific activity directed against a viral target, drug resistant mutants have been used to confirm the mechanism o...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2006.03.004
更新日期:2006-09-01 00:00:00
abstract::While combination antiretroviral therapy (cART) has successfully converted HIV to a chronic but manageable infection in many parts of the world, HIV continues to persist within latent cellular reservoirs, which can become reactivated at any time to produce infectious virus. New therapies are therefore needed not only ...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2018.07.016
更新日期:2018-10-01 00:00:00
abstract::Influenza viruses are major respiratory pathogens responsible for both seasonal epidemics and occasional pandemics worldwide. The current available treatment options have limited efficacy and thus the development of new antivirals is highly needed. We previously reported the identification of a series of cycloheptathi...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2019.03.003
更新日期:2019-05-01 00:00:00