RESUMO
Aiming to fill a gap in the literature, we aimed to identify the most promising EOs blocking in vitro cellular entry of SARS-CoV-2 delta variant without conferring human cytotoxicity and provide insights into the influence of their composition on these activities. Twelve EOs were characterized by gas chromatography coupled to mass spectrometry. The antiviral and cytotoxicity activities were determined using the cell-based pseudoviral entry with SARS-CoV-2 delta pseudovirus and the XTT assay in HeLa cells expressing human angiotensin-converting enzyme 2 (HeLa ACE-2), respectively. Syzygium aromaticum, Cymbopogon citratus, Citrus limon, Pelargonium graveolens, Origanum vulgare, "Illicium verum", and Matricaria recutita showed EC50 lowered or close to 1 µg/mL but also the lowest CC50 (0.20-1.70 µg/mL), except "I. verum" (30.00 µg/mL). Among these, "I. verum", C. limon, P. graveolens and S. aromaticum proved to be promising alternatives for SARS-CoV-2 delta variant inhibition (therapeutic index above 4), which possibly was related to the compounds (E)-anetole, limonene and beta-pinene, citronellol, and eugenol, respectively.
Assuntos
COVID-19 , Óleos Voláteis , Humanos , Óleos Voláteis/farmacologia , SARS-CoV-2 , Células HeLa , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Pixuna virus (PIXV) is an enzootic member of the Venezuelan Equine Encephalitis Virus complex and belongs to the New World cluster of alphaviruses. Herein we explore the role of the cellular cytoskeleton during PIXV replication. We first identified that PIXV undergoes an eclipse phase consisting of 4 h followed by 20 h of an exponential phase in Vero cells. The infected cells showed morphological changes due to structural modifications in actin microfilaments (MFs) and microtubules (MTs). Cytoskeleton-binding agents, that alter the architecture and dynamics of MFs and MTs, were used to study the role of cytoskeleton on PIXV replication. The virus production was significantly affected (p < 0.05) after treatment with paclitaxel or nocodazole due to changes in the MTs network. Interestingly, disassembly of MFs with cytochalasin D, at early stage of PIXV replication cycle, significantly increased the virus yields in the extracellular medium (p < 0.005). Furthermore, the stabilization of actin network with jasplakinolide had no effect on virus yields. Our results demonstrate that PIXV relies not only on intact MTs for the efficient production of virus, but also on a dynamic actin network during the early steps of viral replication.
Assuntos
Alphavirus/fisiologia , Citoesqueleto/virologia , Microtúbulos/virologia , Replicação Viral , Alphavirus/efeitos dos fármacos , Animais , Chlorocebus aethiops , Citocalasina D/farmacologia , Citoesqueleto/efeitos dos fármacos , Depsipeptídeos/farmacologia , Interações Hospedeiro-Patógeno , Microtúbulos/efeitos dos fármacos , Nocodazol/farmacologia , Paclitaxel/farmacologia , Fatores de Tempo , Moduladores de Tubulina/farmacologia , Células VeroRESUMO
Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research.
Assuntos
Anti-Infecciosos Locais/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Doenças Bacterianas Sexualmente Transmissíveis/prevenção & controle , Doenças Virais Sexualmente Transmissíveis/prevenção & controle , Administração Intravaginal , Administração Retal , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/classificação , Anti-Infecciosos Locais/isolamento & purificação , Anti-Infecciosos Locais/toxicidade , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Aprovação de Drogas , Inibidores Enzimáticos/farmacologia , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Herpes Genital/prevenção & controle , Herpes Genital/transmissão , Humanos , Masculino , Estudos Multicêntricos como Assunto , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Tensoativos/farmacologia , Tecnologia Farmacêutica/métodos , Proteínas Virais/antagonistas & inibidores , Internalização do Vírus/efeitos dos fármacosRESUMO
Los microbicidas constituyen una nueva herramienta, todavía en proceso de investigación, que podrían ayudar en la prevención de la infección por los virus de la inmunodeficiencia humana (Human immunodeficiency virus: HIV) y de otras infecciones de transmisión sexual (ITS). Una serie de evidencias ha demostrado que la complejidad de la transmisión sexual de patógenos virales requiere de la identificación de compuestos capaces de bloquear los eventos tempranos del ciclo de infección viral. En este manuscrito hacemos una revisión exhaustiva de las diferentes estrategias que se han estudiado o se están considerando para prevenir ITS mediante el uso de microbicidas, haciendo particular énfasis en aquellos con el potencial de bloquear la infección por el HIV. También se revisa el proceso complejo de evaluación preclínica que se requiere para llegar a estudios en humanos y se concluye con un breve análisis de las estrategias que podrían formar parte del futuro inmediato en la investigación de microbicidas
Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research
Assuntos
Infecções Sexualmente Transmissíveis/prevenção & controle , Fármacos Anti-HIV/análise , Vacinas contra Papillomavirus/análise , Antivirais/uso terapêutico , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/terapia , Herpesvirus Humano 2/efeitos dos fármacos , Anti-Infecciosos/uso terapêuticoRESUMO
Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research.
Assuntos
Anti-Infecciosos Locais/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Doenças Bacterianas Sexualmente Transmissíveis/prevenção & controle , Doenças Virais Sexualmente Transmissíveis/prevenção & controle , Administração Intravaginal , Administração Retal , Animais , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/classificação , Anti-Infecciosos Locais/isolamento & purificação , Anti-Infecciosos Locais/toxicidade , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Aprovação de Drogas , Inibidores Enzimáticos/farmacologia , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Herpes Genital/prevenção & controle , Herpes Genital/transmissão , Humanos , Masculino , Estudos Multicêntricos como Assunto , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Tensoativos/farmacologia , Tecnologia Farmacêutica/métodos , Proteínas Virais/antagonistas & inibidores , Internalização do Vírus/efeitos dos fármacosRESUMO
En el presente trabajo se abordó la obtención de un extracto de la corteza de Aloe vera L., su posterior caracterización y la determinación de la efectividad media frente al virus Herpes simplex tipo 1 (HSV-1). Se concluyó que el extracto obtenido y caracterizado presenta una concentración de antracenderivados totales de 25,0 ± 5,0 mg (por ciento), dicho extracto presenta actividad antiviral in vitro con una toxicidad media de 3,8 ± 0,3 mg/mL y dosis efectiva de 0,80 ± 0,05 mg/mL