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[PMID]:28934457
[Au] Autor:Creanga A; Hang NLK; Cuong VD; Nguyen HT; Phuong HVM; Thanh LT; Thach NC; Hien PT; Tung N; Jang Y; Balish A; Dang NH; Duong MT; Huong NT; Hoa DN; Tho ND; Klimov A; Kapella BK; Gubareva L; Kile JC; Hien NT; Mai LQ; Davis CT
[Ad] Endereço:Influenza Division, Centers for Disease Control and Prevention.
[Ti] Título:Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.
[So] Source:J Infect Dis;216(suppl_4):S529-S538, 2017 Sep 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.
[Mh] Termos MeSH primário: Vírus da Influenza A Subtipo H5N1/isolamento & purificação
Influenza Aviária/epidemiologia
Influenza Humana/epidemiologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Farmacorresistência Viral Múltipla
Genótipo
Técnicas de Genotipagem
Seres Humanos
Vírus da Influenza A Subtipo H5N1/genética
Influenza Aviária/tratamento farmacológico
Influenza Aviária/transmissão
Influenza Humana/tratamento farmacológico
Pandemias
Filogenia
Aves Domésticas/virologia
RNA Viral/genética
Análise de Sequência de RNA
Análise Espaço-Temporal
Vietnã/epidemiologia
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral); 0 (Viral Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix003


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[PMID]:28934455
[Au] Autor:Gubareva LV; Sleeman K; Guo Z; Yang H; Hodges E; Davis CT; Baranovich T; Stevens J
[Ad] Endereço:Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention.
[Ti] Título:Drug Susceptibility Evaluation of an Influenza A(H7N9) Virus by Analyzing Recombinant Neuraminidase Proteins.
[So] Source:J Infect Dis;216(suppl_4):S566-S574, 2017 Sep 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir. The wild-type N9 crystal structure was determined in complex with oseltamivir, zanamivir, or sialic acid, and structural analysis was performed. Results: All substitutions conferred either reduced or highly reduced inhibition by at least 1 NA inhibitor; half of them caused reduced inhibition or highly reduced inhibition by all NA inhibitors. R292K conferred the highest increase in oseltamivir half-maximal inhibitory concentration (IC50), and E119D conferred the highest zanamivir IC50. Unlike N2 (another group 2NA), H274Y conferred highly reduced inhibition by oseltamivir. Additionally, R152K, a naturally occurring variation at the NA catalytic residue of A(H7N9) viruses, conferred reduced inhibition by laninamivir. Conclusions: The recNA method is a valuable tool for assessing the effect of NA changes on drug susceptibility of emerging influenza viruses.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Farmacorresistência Viral Múltipla/genética
Vírus da Influenza A Subtipo H7N9/efeitos dos fármacos
Neuraminidase/antagonistas & inibidores
Proteínas Virais/antagonistas & inibidores
[Mh] Termos MeSH secundário: Ciclopentanos/farmacologia
Bases de Dados Genéticas
Inibidores Enzimáticos/farmacologia
Guanidinas/farmacologia
Seres Humanos
Vírus da Influenza A Subtipo H7N9/genética
Influenza Humana/tratamento farmacológico
Concentração Inibidora 50
Neuraminidase/genética
Oseltamivir/farmacologia
Conformação Proteica
Proteínas Recombinantes/genética
Proteínas Virais/genética
Zanamivir/análogos & derivados
Zanamivir/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Cyclopentanes); 0 (Enzyme Inhibitors); 0 (Guanidines); 0 (R 125489); 0 (Recombinant Proteins); 0 (Viral Proteins); 20O93L6F9H (Oseltamivir); EC 3.2.1.18 (Neuraminidase); L6O3XI777I (Zanamivir); QW7Y7ZR15U (peramivir)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jiw625


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[PMID]:28931216
[Au] Autor:Kiso M; Iwatsuki-Horimoto K; Yamayoshi S; Uraki R; Ito M; Nakajima N; Yamada S; Imai M; Kawakami E; Tomita Y; Fukuyama S; Itoh Y; Ogasawara K; Lopes TJS; Watanabe T; Moncla LH; Hasegawa H; Friedrich TC; Neumann G; Kawaoka Y
[Ad] Endereço:Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo.
[Ti] Título:Emergence of Oseltamivir-Resistant H7N9 Influenza Viruses in Immunosuppressed Cynomolgus Macaques.
[So] Source:J Infect Dis;216(5):582-593, 2017 Sep 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir. Disease severity and mortality were higher in immunosuppressed than in immunocompetent animals. Oseltamivir treatment at 2 different doses reduced A(H7N9) viral titers in infected animals, but even high-dose oseltamivir did not block viral replication sufficiently to suppress the emergence of resistant variants. Some resistant variants were not appreciably attenuated in cultured cells, but an oseltamivir-resistant A(H7N9) virus did not transmit among ferrets. These findings are useful for the control of A(H7N9) virus infections in clinical settings.
[Mh] Termos MeSH primário: Farmacorresistência Viral Múltipla
Hospedeiro Imunocomprometido
Vírus da Influenza A Subtipo H7N9/efeitos dos fármacos
Macaca fascicularis/virologia
Infecções por Orthomyxoviridae/tratamento farmacológico
Oseltamivir/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Antivirais/uso terapêutico
Relação Dose-Resposta a Droga
Feminino
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Vírus da Influenza A Subtipo H7N9/fisiologia
Masculino
Neuraminidase/antagonistas & inibidores
Neuraminidase/metabolismo
Infecções por Orthomyxoviridae/veterinária
Infecções por Orthomyxoviridae/virologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Hemagglutinin Glycoproteins, Influenza Virus); 20O93L6F9H (Oseltamivir); EC 3.2.1.18 (Neuraminidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix296


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[PMID]:28505418
[Au] Autor:Appadurai R; Senapati S
[Ad] Endereço:Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras , Chennai 600 036, India.
[Ti] Título:How Mutations Can Resist Drug Binding yet Keep HIV-1 Protease Functional.
[So] Source:Biochemistry;56(23):2907-2920, 2017 Jun 13.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human immunodeficiency virus-1 (HIV-1) protease is an important drug target for acquired immune deficiency syndrome therapy. Nearly 10 small molecule drugs have been approved by the Food and Drug Administration (FDA). However, prolonged use of these drugs produced protease mutants that are not susceptible to many of these drugs. The mutated proteases, however, continue to cleave the substrate peptides and thus remain largely functional. This poses a major challenge for the treatment strategies. Thus, it has become imperative to understand how these mutations induce drug resistance while maintaining the enzymatic activity of this protein. Here, we perform a comprehensive study of the wild type (WT) and clinically relevant mutated protease bound to a series of FDA-approved drugs and substrates of varying sequences to unravel the mechanism of unhindered activity of the drug-resistant protease variants. Our results from large molecular dynamics simulations suggest that while binding of the substrate to WT and protease mutants involves multiple H-bonding interactions between substrate subsites and the protease's main chain atoms, the drug binds primarily through the hydrophobic interactions with the side chains of protease's active site and flap residues. This implies that any side chain variations caused by mutations in protease could greatly modulate the binding affinity of inhibitors, but not of the substrates. The significantly weaker free energy of binding of the drugs could also be attributed to the limited number of interaction subsites present in the inhibitor structures compared to the substrates. These findings in combination with the identified protease flap and active site residues that contribute to ligand recognition and strong binding can help in the design of future resistance-evading HIV-1 protease inhibitors.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/metabolismo
Protease de HIV/metabolismo
HIV-1/enzimologia
Modelos Moleculares
Mutação
Inibidores de Proteases/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Fármacos Anti-HIV/química
Fármacos Anti-HIV/farmacologia
Sítios de Ligação
Biocatálise
Domínio Catalítico
Bases de Dados de Produtos Farmacêuticos
Bases de Dados de Proteínas
Farmacorresistência Viral Múltipla
Transferência de Energia
Protease de HIV/química
Protease de HIV/genética
HIV-1/efeitos dos fármacos
Seres Humanos
Ligações de Hidrogênio
Interações Hidrofóbicas e Hidrofílicas
Cinética
Ligantes
Conformação Molecular
Simulação de Dinâmica Molecular
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Conformação Proteica
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Ligands); 0 (Protease Inhibitors); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00139


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[PMID]:28446620
[Au] Autor:Garbelli A; Riva V; Crespan E; Maga G
[Ad] Endereço:DNA Enzymology & Molecular Virology Unit, Institute of Molecular Genetics - CNR, via Abbiategrasso 207, Pavia 27100, Italy.
[Ti] Título:How to win the HIV-1 drug resistance hurdle race: running faster or jumping higher?
[So] Source:Biochem J;474(10):1559-1577, 2017 Apr 26.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Infections by the human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), are still totaling an appalling 36.7 millions worldwide, with 1.1 million AIDS deaths/year and a similar number of yearly new infections. All this, in spite of the discovery of HIV-1 as the AIDS etiological agent more than 30 years ago and the introduction of an effective combinatorial antiretroviral therapy (cART), able to control disease progression, more than 20 years ago. Although very effective, current cART is plagued by the emergence of drug-resistant viral variants and most of the efforts in the development of novel direct-acting antiviral agents (DAAs) against HIV-1 have been devoted toward the fighting of resistance. In this review, rather than providing a detailed listing of all the drugs and the corresponding resistance mutations, we aim, through relevant examples, at presenting to the general reader the conceptual shift in the approaches that are being taken to overcome the viral resistance hurdle. From the classic 'running faster' strategy, based on the development of novel DAAs active against the mutant viruses selected by the previous drugs and/or presenting to the virus a high genetic barrier toward the development of resilience, to a 'jumping higher' approach, which looks at the cell, rather than the virus, as a source of valuable drug targets, in order to make the cellular environment non-permissive toward the replication of both wild-type and mutated viruses.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Desenho de Drogas
Farmacorresistência Viral Múltipla
Quimioterapia Combinada
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Modelos Biológicos
[Mh] Termos MeSH secundário: Animais
Fármacos Anti-HIV/efeitos adversos
Fármacos Anti-HIV/química
Fármacos Anti-HIV/farmacologia
Terapia Antirretroviral de Alta Atividade/efeitos adversos
Antagonistas dos Receptores CCR5/química
Antagonistas dos Receptores CCR5/farmacologia
Antagonistas dos Receptores CCR5/uso terapêutico
RNA Helicases DEAD-box/antagonistas & inibidores
RNA Helicases DEAD-box/química
RNA Helicases DEAD-box/genética
RNA Helicases DEAD-box/metabolismo
Quimioterapia Combinada/efeitos adversos
Infecções por HIV/metabolismo
Infecções por HIV/virologia
Inibidores da Protease de HIV/efeitos adversos
Inibidores da Protease de HIV/química
Inibidores da Protease de HIV/farmacologia
Inibidores da Protease de HIV/uso terapêutico
HIV-1/genética
HIV-1/crescimento & desenvolvimento
HIV-1/fisiologia
Interações Hospedeiro-Patógeno/efeitos dos fármacos
Proteínas do Vírus da Imunodeficiência Humana/antagonistas & inibidores
Proteínas do Vírus da Imunodeficiência Humana/química
Proteínas do Vírus da Imunodeficiência Humana/genética
Proteínas do Vírus da Imunodeficiência Humana/metabolismo
Seres Humanos
Estrutura Molecular
Terapia de Alvo Molecular
Mutação
Conformação Proteica
Inibidores da Transcriptase Reversa/química
Inibidores da Transcriptase Reversa/farmacologia
Inibidores da Transcriptase Reversa/uso terapêutico
Fenômenos Fisiológicos Virais/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (CCR5 Receptor Antagonists); 0 (HIV Protease Inhibitors); 0 (Human Immunodeficiency Virus Proteins); 0 (Reverse Transcriptase Inhibitors); EC 3.6.1.- (DDX3X protein, human); EC 3.6.4.13 (DEAD-box RNA Helicases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160772


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[PMID]:28437091
[Au] Autor:Speck-Planche A; Dias Soeiro Cordeiro MN
[Ad] Endereço:LAQV@REQUIMTE/Department of Chemistry and Biochemistry, University of Porto , 4169-007 Porto, Portugal.
[Ti] Título:Speeding up Early Drug Discovery in Antiviral Research: A Fragment-Based in Silico Approach for the Design of Virtual Anti-Hepatitis C Leads.
[So] Source:ACS Comb Sci;19(8):501-512, 2017 Aug 14.
[Is] ISSN:2156-8944
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions, such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen because of the appearance of multidrug resistance (MDR) and the side effects especially associated with long-term treatments. In this work, we report the first multitasking model for quantitative structure-biological effect relationships (mtk-QSBER), focused on the simultaneous exploration of anti-HCV activity and in vitro safety profiles related to the absorption, distribution, metabolism, elimination, and toxicity (ADMET). The mtk-QSBER model was created from a data set formed by 40 158 cases, displaying accuracy higher than 95% in both training and prediction (test) sets. Several molecular fragments were selected, and their quantitative contributions to anti-HCV activity and ADMET profiles were calculated. By combining the analysis of the fragments with positive contributions and the physicochemical meanings of the different molecular descriptors in the mtk-QSBER, six new molecules were designed. These new molecules were predicted to exhibit potent anti-HCV activity and desirable in vitro ADMET properties. In addition, the designed molecules have good druglikeness according to the Lipinski's rule of five and its variants.
[Mh] Termos MeSH primário: Antivirais/química
Simulação por Computador
Descoberta de Drogas/métodos
Hepacivirus/efeitos dos fármacos
Hepatite C/tratamento farmacológico
Relação Quantitativa Estrutura-Atividade
[Mh] Termos MeSH secundário: Antivirais/farmacocinética
Antivirais/toxicidade
Farmacorresistência Viral Múltipla
Modelos Biológicos
Ligação Proteica
Teoria Quântica
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE
[do] DOI:10.1021/acscombsci.7b00039


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[PMID]:28433777
[Au] Autor:Hu Y; Wang Y; Li F; Ma C; Wang J
[Ad] Endereço:Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, United States.
[Ti] Título:Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses.
[So] Source:Eur J Med Chem;135:70-76, 2017 Jul 28.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The efficacy of current influenza vaccines and small molecule antiviral drugs is curtailed by the emerging of multidrug-resistant influenza viruses. As resistance to the only FDA-approved oral influenza antiviral, oseltamivir (Tamiflu), continues to rise, there is a clear need to develop the next-generation of antiviral drugs. Since more than 95% of current circulating influenza A viruses carry the S31N mutation in their M2 genes, the AM2-S31N mutant proton channel represents an attractive target for the development of broad-spectrum antivirals. In this study we report the design and synthesis of the first class of organosilanes that have potent antiviral activity against a panel of human clinical isolates of influenza A viruses, including viruses that are resistant to amantadine, oseltamivir, or both.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Desenho de Drogas
Farmacorresistência Viral Múltipla/efeitos dos fármacos
Vírus da Influenza A/efeitos dos fármacos
Silanos/farmacologia
[Mh] Termos MeSH secundário: Antivirais/síntese química
Antivirais/química
Relação Dose-Resposta a Droga
Seres Humanos
Testes de Sensibilidade Microbiana
Estrutura Molecular
Silanos/síntese química
Silanos/química
Relação Estrutura-Atividade
Proteínas da Matriz Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (M2 protein, Influenza A virus); 0 (Silanes); 0 (Viral Matrix Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170424
[St] Status:MEDLINE


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[PMID]:28418652
[Au] Autor:Ghosh AK; Rao KV; Nyalapatla PR; Osswald HL; Martyr CD; Aoki M; Hayashi H; Agniswamy J; Wang YF; Bulut H; Das D; Weber IT; Mitsuya H
[Ad] Endereço:Department of Chemistry and Department of Medicinal Chemistry, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
[Ti] Título:Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown-Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV Variants.
[So] Source:J Med Chem;60(10):4267-4278, 2017 May 25.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1 protease inhibitors are reported. Inhibitor 5 displayed superior antiviral activity and drug-resistance profiles. In fact, this inhibitor showed several orders of magnitude improved antiviral activity over the FDA approved drug darunavir. This inhibitor incorporates an unprecedented 6-5-5 ring-fused crown-like tetrahydropyranofuran as the P2 ligand and an aminobenzothiazole as the P2' ligand with the (R)-hydroxyethylsulfonamide isostere. The crown-like P2 ligand for this inhibitor has been synthesized efficiently in an optically active form using a chiral Diels-Alder catalyst providing a key intermediate in high enantiomeric purity. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.
[Mh] Termos MeSH primário: Desenho de Drogas
Inibidores da Protease de HIV/química
Inibidores da Protease de HIV/farmacologia
Protease de HIV/metabolismo
HIV-1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Benzotiazóis/química
Benzotiazóis/farmacologia
Cristalografia por Raios X
Farmacorresistência Viral Múltipla
Furanos/química
Furanos/farmacologia
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
Protease de HIV/química
HIV-1/química
HIV-1/metabolismo
Seres Humanos
Ligantes
Simulação de Acoplamento Molecular
Piranos/química
Piranos/farmacologia
Relação Estrutura-Atividade
Sulfonamidas/química
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzothiazoles); 0 (Furans); 0 (HIV Protease Inhibitors); 0 (Ligands); 0 (Pyrans); 0 (Sulfonamides); 0 (aminobenzothiazole compound); EC 3.4.23.- (HIV Protease); EC 3.4.23.- (p16 protease, Human immunodeficiency virus 1)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00172


  9 / 985 MEDLINE  
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Tanuri, Amilcar
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[PMID]:28333295
[Au] Autor:Andrade SD; Sabidó M; Monteiro WM; Benzaken AS; Tanuri A
[Ad] Endereço:Tropical Medicine Foundation Doctor Heitor Vieira Dourado (FMT-HVD), Av. Pedro Teixeira 25, Manaus, Amazonas, CEP: 69040-000, Brazil.
[Ti] Título:Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas.
[So] Source:J Antimicrob Chemother;72(6):1774-1783, 2017 Jun 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil. Methods: Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses. Results: One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%). Conclusions: We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacologia
Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral Múltipla/genética
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
HIV-1/genética
[Mh] Termos MeSH secundário: Terapia Antirretroviral de Alta Atividade
Brasil
Criança
Pré-Escolar
Estudos de Coortes
Feminino
Genótipo
Infecções por HIV/epidemiologia
Infecções por HIV/transmissão
HIV-1/isolamento & purificação
Seres Humanos
Lactente
Transmissão Vertical de Doença Infecciosa
Masculino
Mães
Mutação
Filogenia
RNA Viral/sangue
RNA Viral/genética
Estudos Retrospectivos
Análise de Sequência de DNA
Carga Viral
Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (RNA, Viral); 0 (pol Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkx025


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[PMID]:28333232
[Au] Autor:Assoumou L; Charpentier C; Recordon-Pinson P; Grudé M; Pallier C; Morand-Joubert L; Fafi-Kremer S; Krivine A; Montes B; Ferré V; Bouvier-Alias M; Plantier JC; Izopet J; Trabaud MA; Yerly S; Dufayard J; Alloui C; Courdavault L; Le Guillou-Guillemette H; Maillard A; Amiel C; Vabret A; Roussel C; Vallet S; Guinard J; Mirand A; Beby-Defaux A; Barin F; Allardet-Servent A; Ait-Namane R; Wirden M; Delaugerre C; Calvez V; Chaix ML; Descamps D; Reigadas S; ANRS AC-11 Resistance Study Group
[Ad] Endereço:Sorbonne Universités, UPMC Univ. Paris 06, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP UMRS 1136), F75013 Paris, France.
[Ti] Título:Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study.
[So] Source:J Antimicrob Chemother;72(6):1769-1773, 2017 Jun 01.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral Múltipla
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
HIV-1/efeitos dos fármacos
Carga Viral
[Mh] Termos MeSH secundário: Adulto
Terapia Antirretroviral de Alta Atividade
Feminino
França
Genes Virais
Genótipo
Infecções por HIV/sangue
Integrase de HIV/sangue
Integrase de HIV/genética
Protease de HIV/sangue
Protease de HIV/genética
Transcriptase Reversa do HIV/sangue
Transcriptase Reversa do HIV/genética
HIV-1/genética
Seres Humanos
Masculino
Meia-Idade
RNA Viral/sangue
Inibidores da Transcriptase Reversa/uso terapêutico
Análise de Sequência de DNA
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (RNA, Viral); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.- (HIV Integrase); EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1); EC 2.7.7.49 (HIV Reverse Transcriptase); EC 3.4.23.- (HIV Protease)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkx042



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