Arboviruses represent a contemporary global challenge, prompting coordinated efforts from health organizations and governments worldwide. Dengue, chikungunya, and Zika viruses have become endemic in the tropics, resulting in the so-called “triple arbovirus epidemic”. These viruses are transmitted typically through the bites of infected mosquitoes, especially A. aegypti and A. albopictus. These mosquito species are distributed across all continents and exhibit a high adaptive capacity in diverse environments. When combined with unplanned urbanization, uncontrolled population growth, and international travel—the so-called “triad of the modern world”—the maintenance and spread of these pathogens to new areas are favored. This review provides updated information on vaccine candidates targeting dengue, chikungunya, and Zika viruses. Additionally, we discuss the challenges, perspectives, and issues associated with their successful production, testing, and deployment within the context of public health.
Arthropod-borne viruses within the Flaviviridae family such as Zika (ZIKV) and dengue (DENV) are responsible for major outbreaks in tropical countries, and there are no specific treatments against them. Naringenin and 7-O-methyl naringenin are flavonoids that can be extracted from geopropolis, a natural material that the Brazilian Jandaira stingless bee (Melipona subnitida Ducke) produces to protect its nest. Here, these flavonoids were tested against ZIKV and DENV using Vero cells as a cellular model to perform a cytotoxicity assay and to define the effective concentrations of TCID50 as the readout method. The results demonstrated the antiviral activity of the compounds against both viruses upon the treatment of infected cells. The tested flavonoids had antiviral activity comparable with 6-methylmercaptopurine riboside (6-MMPr), used here as a positive control. In addition, to identify the possible action mechanism of the antiviral candidates, we carried out a docking analysis followed by a molecular dynamics simulation to elucidate naringenin and 7-O-methyl naringenin binding sites to each virus. Altogether, these results demonstrate that both flavonoids have potent antiviral effects against both viruses and warrant further in vivo trials.
Cellular components and inflammatory mediators involved in the transmigration of HTLV-1-infected cells across the blood–brain barrier (BBB) are not fully understood. This study proposes a BBB model to identify the immunological mechanisms associated with HTLV-1 pathogenesis. PBMCs from individuals with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) (n = 4) or HTLV-1-infected individuals without HAM/TSP (n = 4) were isolated. An indirect cell co-culture was performed between human brain microvascular endothelial (hBMEC) cells and neuroblastoma (SH-SY5Y) cells. PBMCs from healthy individuals (n = 4) were used as a negative control, and MT-2 cells were used as a positive control. Supernatants and cells were collected to quantify inflammatory cytokines and assess cell death after 24, 48, and 72 h. Multiple comparisons were performed using the Kruskal–Wallis test, followed by Fisher’s LSD post hoc analysis. We observed that the production of cytokines IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, as well as the rate of neuronal death, was higher in co-cultures mimicking HAM/TSP carriers compared to HTLV-1-infected individuals without HAM/TSP and controls. Our results suggest that the HAM/TSP condition induces the release of IL-6, IL-8, IL-1β, TNF, IL-10, and IL-12p70, along with the infiltration of mononuclear cells, which may lead to neuronal death.