Análisis del efecto del Candesartán en la replicación in vitro del virus dengue en un modelo de potenciación de la infección mediado por anticuerpos

Abstract

Dengue is an arthropod-borne viral infection and represents a public health problem in tropical and subtropical areas. As in many other Latin American countries, the Colombian population has been severely affected by dengue; in fact, approximately 2.0% of reported dengue cases in the Americas occur in Colombia [1]. Dengue results from infection by one of four virus serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. This virus belongs to the Flaviviridae family and is transmitted to humans through the bite of Aedes aegypti mosquitoes. The clinical manifestations of dengue vary from a mild flu-like syndrome to a more severe form of the disease (DHF or DSS) [2]. At present, there is no specific treatment for dengue, its therapeutic management is directed to the treatment of symptoms, however, dengue vaccine is available. Despite this, the existence of multiple serotypes of DENV and the underlying mechanism leading to DHF and DSS could seriously limit the overall efficacy of the vaccine and the health of patients [3]. Recently, Candesartan, an antihypertensive drug, has been shown to exert antiviral effects by inhibiting dengue and Zika virus replication in primary infection models. Due to the need for an effective treatment for dengue and considering the possible antiflavivirus effects of Candesartan, the present research work focused on the study of the effect of this drug on dengue virus replication in vitro in an antibody-mediated potentiation model of infection. For this purpose, the K562 cell line was used, which resembles conditions that allow the study of secondary infections, which are the main risk factor for the development of severe dengue. For this, the 4G2 antibody and the four serotypes of the virus were used, using analytical methods such as flow cytometry. The results obtained suggest that Candesartan possesses antiviral activity against the DENV-1 serotype, since a significant change in the percentage reduction of infection was observed when the five concentrations of Candesartan (5, 10, 20, 40 and 80 μM) were used.