RESUMO
Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 µg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC50 of 4.1 and 17.2 µg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively.
Assuntos
Antivirais/farmacologia , Polissacarídeos/farmacologia , Rodófitas/química , Adsorção/efeitos dos fármacos , Animais , Antivirais/análise , Antivirais/química , Antivirais/isolamento & purificação , Sobrevivência Celular , Chlorocebus aethiops , Galactose/análogos & derivados , Galactose/química , Galactose/farmacologia , HIV-1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Metaloproteinase 17 da Matriz/efeitos dos fármacos , Peso Molecular , Marrocos , Oceanos e Mares , Fitoterapia , Preparações de Plantas/farmacologia , Polissacarídeos/análise , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Sulfatos/química , Sulfatos/farmacologia , Fatores de Tempo , Ácidos Urônicos/química , Ácidos Urônicos/farmacologia , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
The construction of a recombinant antibody directed against the cellular epitope R7V acquired by HIV during the viral budding has been realized. The c-DNAs encoding the variable regions of the anti-R7V antibody have been cloned from B lymphocytes of a non-progressor patient. Two transfer vectors containing complete coding sequences for heavy and light chains of this antibody were constructed and a recombinant baculovirus was generated by a double recombination between baculovirus DNA and the two transfer vectors. Insect cells infected with this baculovirus produced a complete human anti-R7V immunoglobulin. This recombinant antibody, specific to the R7V peptide, recognizes and neutralizes all clades of HIV1 including resistant viruses, opening new perspectives in anti-HIV therapy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Anti-HIV/uso terapêutico , Infecções por HIV/terapia , Microglobulina beta-2/imunologia , Sequência de Aminoácidos , Animais , Terapia Antirretroviral de Alta Atividade , Baculoviridae/genética , Sequência de Bases , Linhagem Celular , HIV-1/imunologia , Humanos , Dados de Sequência Molecular , Testes de Neutralização , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/uso terapêutico , Spodoptera , Falha de TratamentoRESUMO
Many attempts to use therapeutic antibodies to treat HIV have been unsuccessful owing to the high variability of the viral proteins, the multiplicity of the cellular targets, and the conformational changes of the gp120 glycoprotein during cell binding. A new concept of identifying a cellular antigen associated with the HIV envelope was investigated. The characterized epitope, R7V, is responsible for the formation of antibodies protective against HIV in non-progressor patients. The purified anti-R7V antibodies neutralize all HIV isolates, including the escape mutants after highly active antiretroviral therapy, creating a new therapeutic tool for the treatment of HIV-infected patients.
Assuntos
Anticorpos Anti-HIV/isolamento & purificação , Anticorpos Anti-HIV/uso terapêutico , Infecções por HIV/terapia , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral Múltipla , Epitopos , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Imunoterapia Ativa/métodos , Falha de TratamentoRESUMO
Starting from the chemical structure of the recent FDA-approved anti-HIV drug Amprenavir (Agenerase), a potent HIV-protease inhibitor, we have designed new series of Amprenavir bioisoteres in which the methylene group of the benzyl group was replaced by a sulfur atom. This structural modification has required an original multistep synthesis. Unfortunately, introduction of the sulfur atom abolished or drastically decreased both inhibitory activity on recombinant HIV protease and HIV infection protection on MT4 cell cultures.
Assuntos
Fármacos Anti-HIV/síntese química , Inibidores da Protease de HIV/síntese química , Sulfonamidas/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Carbamatos , Linhagem Celular , Furanos , Protease de HIV/metabolismo , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Estereoisomerismo , Relação Estrutura-Atividade , Replicação ViralRESUMO
A cepa MN do HIV-1 e conhecida por ser mais prevalente no Brasil, a cepa BRU e mais prevalente na Europa e a cepa NDK na Africa. Tem sido sugerido na literatura que diferentes cepas devam ser incluidas em uma mesma vacina contra o HIV-1. Com o intuito de se contribuir para o desenvolvimento de uma vacina universal, a ocorrencia de anticorpos (Ac) contra tres cepas do HIV-1 (MN, BRU, NDK) foram determinadas em amostras de soros de 85 pacientes voluntarios, adultos, soropositivos para o HIV-1, atendidos em um Hospital Universitario. Cem unidades infectantes para cultura de tecido (TCIU) dos virus reagiram com diluicoes seriadas de soro (2x) e celulas MT4 adicionadas a uma concentracao final de 0,3 x 10 elevado a sexta potencia celulas/ml...
Assuntos
Humanos , Masculino , Feminino , Anticorpos Anti-HIV , Infecções por HIV/diagnóstico , Testes de Neutralização/métodos , Técnicas de Cultura , HIV-1/imunologia , Grupos de RiscoRESUMO
Acquired immune deficiency syndrome (AIDS) is an epidemic immunesuppresivbe disease characteristically associated with a depletion of T4 lymphocytes of the helper phenotype. A virus currently named HIV (human immune deficiency virus_ was repeatedly isolated from lymphocytes from patients with AIDS of from those atrisk for the disease. HIV is a retovirus provisionally included in the Lentiviruses subfamily because it shares properties in common with Visna-Maed virus, like ability to cause slow infection, cell fusion and other cythopathic effects in cultured cells. The AIDS virus homes to a receptor on the surface of helper T cells. Circulating antibodies to HIV can be detected in sera from AIDS patients and people in various high risk groups. Eight five percent of asymptomatic carriers harbour the virus in the presence of antibodies. Virus and antibodies are also present in patients with generalized lymphadenopathies, a state of ARC (AIDS related complexes) and in AIDS patients who suffered opportunistic infections or Kaposi sarcoma
Assuntos
Humanos , HIV/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/etiologia , Efeito Citopatogênico Viral , HIV/genética , HIV/imunologia , HIV/ultraestrutura , Linfócitos T Auxiliares-Indutores , Linfócitos T/imunologiaRESUMO
Acquired immune deficiency syndrome (AIDS) is an epidemic immunesuppresivbe disease characteristically associated with a depletion of T4 lymphocytes of the helper phenotype. A virus currently named HIV (human immune deficiency virus_ was repeatedly isolated from lymphocytes from patients with AIDS of from those atrisk for the disease. HIV is a retovirus provisionally included in the Lentiviruses subfamily because it shares properties in common with Visna-Maed virus, like ability to cause slow infection, cell fusion and other cythopathic effects in cultured cells. The AIDS virus homes to a receptor on the surface of helper T cells. Circulating antibodies to HIV can be detected in sera from AIDS patients and people in various high risk groups. Eight five percent of asymptomatic carriers harbour the virus in the presence of antibodies. Virus and antibodies are also present in patients with generalized lymphadenopathies, a state of ARC (AIDS related complexes) and in AIDS patients who suffered opportunistic infections or Kaposi sarcoma (AU)
