Comparative screening of anti-dengue activity in aqueous and ethanol extracts of mangrove plants from Sabah

Aims@#Dengue virus is a global pathogen that lacks an effective vaccine or therapy. Screening medicinal plants for anti-dengue properties provides a promising avenue to identify potent compounds. Mangroves, known for their resilience in harsh conditions, produce a diverse range of natural products with unique biochemical profiles, which hold potential for anti-dengue treatments. This study aims to evaluate the anti-dengue activity of selected mangrove plant species from Sabah against DENV2 NS2B-NS3pro, utilizing an enzymatic protease assay. @*Methodology and results @#Six mangrove species (Avicennia marina, Bruguiera gymnorrhiza, Ceriops tagal, Rhizophora apiculata, Rhizophora mucronata and Xylocarpus granatum) were investigated, with various plant parts subjected to aqueous and ethanol extraction. The results demonstrated significant anti-dengue activity in both aqueous and ethanolic extracts of the mangroves against DENV2 NS2B-NS3pro, with IC50 values ranging from 0.95 µg/mL to 6.24 µg/mL. Notably, the ethanolic extract of R. apiculata leaves exhibited the highest inhibition, with an IC50 value of 0.95 µg/mL. @*Conclusion, significance and impact of study@#These findings suggest that the ethanolic extracts from R. apiculata leaves hold promise as potential candidates for dengue treatment. This study underscores the importance of natural products as valuable sources for the development of novel anti-dengue treatments, highlighting the need to explore mangroves in the quest for effective therapeutic options.

Metodología de pesquisa primaria de actividad antidengue a partir de productos naturales / Methodology for primary screening of antidengue activity based on natural products

Introducción: El virus dengue, transmitido por mosquitos del género Aedes ha reemergido en los últimos años produciendo la enfermedad transmitida por artrópodos con mayor prevalencia en humanos, y no existe una terapia antiviral específica ni vacunas, para su tratamiento y prevención. Ello ha motivado la búsqueda de productos y compuestos naturales con actividad antiviral, lo cual trae consigo la necesidad de establecer un sistema de evaluación de productos naturales y sintéticos mediante una metodología de pesquisa rápida in vitro. Objetivo: Proponer un sistema de pesquisa primaria de actividad antiviral contra el virus dengue basado en células. Métodos: Se utilizaron como fuentes primarias de información trabajos publicados en revistas nacionales e internacionales registradas en las bases de datos SciELO o PubMed. Los ejemplos seleccionados en las figuras y tabla proceden de las publicaciones conjuntas del Grupo de Virología de la Facultad de Biología de la Universidad de La Habana y del Laboratorio de Arbovirus del Instituto de Medicina Tropical Pedro Kourí. Información, análisis y síntesis: Se presentan las principales metodologías basadas en células, y se enfatiza en aquellas asumidas por nuestro grupo (evaluación de la citotoxicidad y el ensayo primario de actividad antiviral). Se muestra el algoritmo de evaluación de un producto. La metodología descrita ha permitido poner en marcha un programa de búsqueda de fármacos antidengue, teniendo en cuenta los criterios de la evaluación de la eficacia antiviral y la toxicidad, para realizar un estudio posterior de mecanismo de acción de los diferentes compuestos o productos evaluados.

Introduction: Dengue virus, transmitted by Aedes specie mosquitos, has re-emerged in the last years causing the arthropod-borne disease with higher prevalence in humans, to which there is no specific antiviral therapy or vaccine for its treatment and prevention. This has motivated the search for natural-based products with antiviral activity, which implies the need to establish an evaluation system of natural and synthetic products through a rapid in vitro screening methodology. Objective: To propose a primary screening cell-based antiviral activity system against dengue virus. Methods: Papers published in national and international journals indexed in SciELO or PubMed were used as primary sources of information. The examples selected in the figures and table were retrieved from the joint publications of the Virology Group of the School of Biology of the University of Havana and the Arbovirus Laboratory of the Institute of Tropical Medicine Pedro Kourí. Information, Analysis and Synthesis: The main cell-based methodologies are presented, with emphasis on those assumed by our research group (evaluation of cytotoxicity and the primary antiviral activity assay). The algorithm for product evaluation is presented. The methodology described has allowed initiating a search program for antidengue drugs, taking into account the criteria for evaluating antiviral efficacy and toxicity, in order to carry out a subsequent study on the mechanisms of action of the different compounds or products evaluated.

Avances en la investigación del virus dengue en Colombia: papel de los microARNs celulares en la respuesta anti-dengue virus / Advances in dengue virus research in Colombia: the role of cellular microRNAs as an anti-dengue virus response

Dengue is one of the most important mosquito-borne diseases, and its incidence has increased at an alarming rate in recent years, becoming a real public health problem. Currently, there is no vaccine or medication or proper treatment for dengue control. Considering this situation, it is necessary to prioritize the search for new alternatives and strategies for dengue prevention and control, in order to reduce not only the economic burden of endemic countries, but also to improve the quality of life of patients. In this regard, a brief reflection on some aspects related to the search for new alternatives in Colombia is presented. This is focused on the use of microRNAs, which could be a new strategy with great therapeutic potential.

El dengue es una de las enfermedades más importantes transmitidas por mosquitos y su incidencia ha aumentado a un ritmo alarmante en los últimos años, al punto que se ha convertido en un verdadero problema de salud pública. Actualmente no existe ni vacuna, ni un medicamento o tratamiento adecuado para el control del dengue. Con dichos antecedentes, es necesario priorizar en la búsqueda de nuevas alternativas o estrategias de control y prevención del dengue con miras a disminuir no sólo la carga económica de los países endémicos, sino también a mejorar la calidad de vida de los pacientes. En este sentido, se presenta una breve reflexión sobre algunos aspectos relacionados con la búsqueda de nuevas alternativas en Colombia, enfocadas en el uso de los microARNs, que podrían constituir una nueva estrategia con un gran potencial terapéutico, dado que tendrían el potencial de contrarrestar algunas infecciones virales crónicas.

Research Progress of Chemical Drugs Against Dengue Virus / 中国药学杂志

Dengue fever is one of the most important vector-borne human diseases caused by mosquito vectorAedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome. There are no approved drugs for the treatment of dengue disease so far. According to the mechanism of anti-dengue virus(anti-DENV) action, drugs under development for dengue disease can be divided into two categories: viral replication inhibitors and anti-cell factor pathway inhibitors. The former is further divided into DENV entry inhibitors, capsid protein inhibitors, NS3 protein inhibitors, NS5 protein inhibitors, and NS4B protein inhibitors; the latter is further divided into cell receptor inhibitors, lipid synthesis and metabolism inhibitors, and glucosidase inhibitors. The R&D of anti-DENV drugs is facing enormous challenges. Development of effective drugs which can be used for the treatment of four serotypes of dengue has a broad application prospect, and it will bring new hopes for dengue fever prevention and therapy.

Research on chemical constituents from Re-Du-Ning Injection (III) / 中草药

Objective: To study the antiviral constituents from the active fraction of Re-Du-Ning (RDN) Injection. Methods: In this study, the active fraction of RDN Injection was screened by the mice model loaded with restraint stress infected with influenza virus. The chemical constituents were isolated by chromatography on silica gel, ODS, Sephadex LH-20 & Toyopearl HW-40 columns, and reverse phase MPLC & HPLC repeatedly. Their structures were identified by spectral data and physicochemical property. Results: The 95% ethanol eluate of RDN Injection on the macroporous adsorption resin column was proved to be the antivirus active fraction of RDN Injection. Fourteen compounds were isolated and identified as (2E,6S)-8-[α-L-arabinopyranosyl-(1″-6')-β-D-glucopyranosyloxy]- 2,6-dimethylct-2-eno-1,2″-lactone (1), lyoniresinol (2), 5'-methoxyisolariciresinol (3), ent-isolariciresinol (4), (7R,8R)-4,7,9,9'- tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (5), (7S,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (6), ceplignan (7), 5'-methoxyceplignan (8), (-)-dihydrodehydrodiconiferyl alcohol (9), (7S,8R)-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan-4,9,9'-triol (10), (2-cis, 4-trans)-abscisic acid (11), (2-trans, 4-trans)-abscisic acid (12), (1S,3R,4R,5S,7R,9R)-decane-6-carboxylic acid (13), and (1S,3R,4S,5S,7R,9R)-decane-6-carboxylic acid (14); Among them, compound 1 exhibited the antivirus activity against Dengue virus. Conclusion: Compound 8 is a new compound and the other isolated compounds are reported from RDN Injection for the first time, and compound 1 shows the anti-virus activity against Dengue virus.

Purification and characterization protein of anti-dengue specific immunoglobulin Y for diagnostic kit of dengue.

This study aimed to produce immunoglobulin Y (IgY) specific to dengue virus which could be used for diagnostic kit of dengue. Lohman laying hens were immunized intramuscularly with antigenic of dengue. Egg yolk was separated from egg white and IgY antibody was then purified by multiple polyethylene glycol (PEG) 6000 extraction and ammonium sulfate purification steps. The IgY concentration in egg yolk increased during the immunization period until week 6 where it began to increase dramatically at 2 weeks and it reached a plateau at 4 weeks after immunization. After week 6 the levels decreased gradually. Antibody of dengue was detected and produce a specific line of precipitation in agar gel precipitation test (AGPT) beginning the second week after the first immunization. Analysis of results obtained with ELISA showed significant increase in the denguespecific antibodies after two weeks from the primary immunization. Through the effect of boostering; the antidengue antibody levels reached a plateau at four weeks from the primary immunization and remained significantly higher till the end of observation period. SDS-PAGE revealed the IgY preparation to be pure and dissociated into protein bands with molecular weights of 145; 66; 45, 33 and 26 kDa and western blot analysis revealed the presence of anti-dengue IgY in egg yolks protein, with a molecular weights of approximately 66 kDa. These results suggested that chicken IgY could be a practical strategy in large-scale production of specific anti-dengue Ig Y for diagnostic KIT of dengue.

Nuevas evidencias en la susceptibilidad a la infección por dengue asociadas al polimorfismo HH del receptor FcgRIIa / New evidence in the susceptibility to dengue infection associated to HH polymorphism of FcgRlla receptor

Introducción: las variantes polimórficas del receptor FcgR IIa han sido asociadas con la susceptibilidad a padecer diferentes enfermedades infecciosas. Recientemente se reportó la asociación entre el polimorfismo de este receptor y la susceptibilidad a padecer la fiebre hemorrágica por dengue. Objetivos: explorar si la asociación a la susceptibilidad o protección de las variantes homocigóticas del receptor, pudieran estar relacionadas además, con los títulos de IgG y la exposición a diferente número de infecciones. Métodos: se hizo un estudio de tipo analítico retrospectivo a individuos infectados por virus dengue 4 en Ciudad de La Habana durante la epidemia de 2006, que se contactaron en 2008. Se reclutó un total de 97 individuos, de los cuales 68 habían padecido fiebre dengue y 29 fiebre hemorrágica de dengue.Se les extrajo una muestra de 10 mL de sangre total en anticoagulante que se empleó en el aislamiento de ADN. Se determinó el polimorfismo genético del receptor FcgRIIa, los títulos de anticuerpos totales IgG anti-dengue y el antecedente de infección por dengue. Resultados: se evidenció, de modo interesante, una relación directamente proporcional y muy significativa (p< 0,0001) entre los altos títulos de IgG anti-dengue con el número de infecciones padecidas. Este comportamiento fue característico en los individuos con la variante homocigótica HH. Conclusiones: al parecer, en aquellos individuos con polimorfismo para el receptor FcgRIIa-H/H podría haber una tendencia a la no eliminación de los anticuerpos IgG a través del FcgRIIa, la cual está asociada con el número de infecciones.

Introduction: polymorphic variants of FcgRIIa receptor have been associated to susceptibility to develop several infectious diseases. The relationship between the polymorphism of this receptor and the susceptibility to dengue hemorrhagic fever was recently reported. Objectives: to explore whether the association of the homocygotic variants of the receptor to susceptibility to or protection from a disease could be also related with the IgG antibody titters and the exposure to a number of infections. Methods: a retrospective analytical study was performed on individuals who had been infected with the dengue virus 4 during the 2006 epidemic in the City of Havana and were tracked down in 2008. A total number of 97 individuals were recruited of whom 68 had suffered dengue fever and 29 had had dengue hemorrhagic fever. A 10 mL blood sample was taken from each of them and then placed in EDTA anticoagulant for DNA isolation and 5ml placed in dry tubes to obtain serum. The genetic polymorphism of FcgRlla receptor, the total anti-dengue IgG antibody titers and the antecedent of dengue infection were determined. Results: it was interesting to note that there was very significant direct relation (p< 0.0001) between high anti-dengue IgG antibodies titers and the number of infections suffered by these people. This behaviour was present in those individuals with the HH homocygotic variant. Conclusion: it seems that those individuals with polymorphism in FCgRlla-H/H receptor would tend to non-elimination of IgG antibodies through this receptor, which is associated to the number of infections suffered by the individual.