ABSTRACT
Latência e resistência de cepas de Herpes simples tipo 1 (HSV-1) ao aciclovir têm sido associados a sequelas graves em pacientes imunocomprometidos, como pacientes com AIDS. Por essa razão, a pesquisa por novas substâncias com atividade anti-HSV-1 é uma necessidade urgente. Objetivo: Investigar se os extratos obtidos de Plexaurella spp poderiam ser usados em estudos pré-clínicos de drogas contra o vírus herpes simples tipo 1. Métodos: A viabilidade celular e concentrações inibitórias das drogas foram utilizados como testes de triagem para investigar os extratos etil acetato e diclorometano de Plexaurella spp como antivirais. Resultados: Os resultados de viabilidade demonstraram que os extratos de Plexaurella regia e Plexaurella grandflora não foram citotóxicas, mas somente Plexaurella regia alcançou um valor de CC50 expressivo. Nos ensaios antivirais, Plexaurella regia mostraram um resultado ainda mais significante de concentração efetiva (EC50) e índice terapêutico (<2.5 µg/mL e 51.6 µg/mL, respectivamente) comparado com aciclovir (ACV). Conclusão: Estes resultados mostram que os extratos de corais têm atividade anti-herpética e podem contribuir para novas estratégias de redução da incidência de resistência de doenças relacionadas aos herpes vírus
Latency and resistance of acyclovir-resistant strains of Herpes simplex virus type 1 (HSV-1) have been associated with serious sequelae in immunocompromised individuals, such as AIDS patients. Consequently, the search for new substances with anti-HSV activity is both necessary and urgent. Objective: To investigate whether extracts obtained from Plexaurella spp can be used in preclinical studies of drugs against herpes simplex virus type 1. Methods: Cell viability and inhibitory drug concentrations as screening tests were used to investigate ethyl acetate and dichloromethane extracts from Plexaurella spp as antivirals. Results: The results of viability assays demonstrated that extracts from Plexaurella regia and Plexaurella grandiflora showed less cytotoxicity, but only Plexaurella regia reached a very expressive CC50 value. In antiviral assays, Plexaurella regia showed an even more significant result of effective concentration (EC50) and therapeutic index (<2.5 µg/mL and 51.6 µg/mL, respectively) compared with acyclovir (ACV). Conclusion: These results demonstrated that extracts from corals have anti-herpetic activities and could contribute towards new strategies to stop the increasing incidence of resistance in herpes-related diseases.
Subject(s)
Humans , Antiviral Agents , Biological Products , Drug Resistance , Herpesvirus 1, Human , Virus ReplicationABSTRACT
Bovine viral diarrhea virus (BVDV) is an etiologic agent that causes important economic losses in the world. It is endemic in cattle herds in most parts of the world. The purpose of this study was to evaluate the in vitro cytotoxic effect and antiviral properties of several marine natural products obtained from seaweeds: the indole alkaloid caulerpin (CAV, 1) and three diterpenes: 6-hydroxydichotoma-3,14-diene-1,17-dial (DA, 2), 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene (DB1, 3) and 8,10,18-trihydroxy-2,6-dolabelladiene (DB3, 4). The screening to evaluate the cytotoxicity of compounds did not show toxic effects to MDBK cells. The antiviral activity of the compounds was measured by the inhibition of the cytopathic effect on infected cells by plaque assay (PA) and EC50 values were calculated for CAV (EC=2,0± 5.8), DA (EC 2,8± 7.7), DB1 (EC 2,0±9.7), and DB3 (EC 2,3±7.4). Acyclovir (EC50 322± 5.9) was used in all experiments as the control standard. Although the results of the antiviral activity suggest that all compounds are promising as antiviral agents against BVDV, the Selectivity Index suggests that DB1 is the safest of the compounds tested.
ABSTRACT
About 80% of the human adult population is infected with HSV-1. Although there are many anti-HSV-1 drugs available (acyclovir, ganciclovir, valaciclovir, foscarnet), their continuous use promotes the selection of resistant strains, mainly in ACV patients. In addition to resistance, the drugs also have toxicity, particularly when administration is prolonged. The study of new molecules isolated from green algae with potential antiviral activity represents a good opportunity for the development of antiviral drugs. Caulerpin, the major product from the marine algae Caulerpa Lamouroux (Caulerpales), is known for its biological activities such as antioxidant, antifungal, acetylcholinesterase inhibitor (AChE) and antibacterial activity. In this work, we show that caulerpin could be an alternative to acyclovir as an anti-HSV-1 drug that inhibits the alpha and beta phases of the replication cycle.
ABSTRACT
Dolabelladienotriol is a product extracted from the brown marine alga Dictyota pfaffii from Brazil that has been shown to have antiviral activity and low cytotoxicity. Our studies have evaluated the acute toxicity of dolabelladienotriol in BALB/c mice for ten days after administration of a single dose. Among the parameters considered were behavior, weight, biochemical and histological analyses of blood samples taken at three different times (Bs.0, Bs.1 and Bs.2) and optical microscopic examination of organs like liver, kidney, stomach and small intestine. Mice deaths were not observed at any dose during the ten day period. There were some changes in the biochemical analysis results for urea nitrogen (BUN) and alanine aminotransferase (ALT), but the changes were not significantly different from the reference levels of the animals before administration of the substance. Histological analyses of tissues were very similar for all animals. The alterations in liver and kidney tissues did not affect the animals´ behavior at any concentration, not even at 50 mg/kg, where the most significant changes in tissues were seen. This study indicates that dolabelladienotriol has low toxicity in administered dose range.