Objectives
Dengue virus surface proteins are often used in the development of vaccines that protect against dengue virus infection. However, the surface proteins on the four serotypes of dengue virus display high variation, which increases the difficulty of developing a vaccine that can protect against all viral strains. In this study, a polytope that is recognized by broadly neutralizing antibodies (bnAbs) was designed using conserved epitopes from the four serotypes.
Methods
We constructed a polytope using four conserved dengue virus epitopes such that two aligned epitopes were separated from the other two epitopes by a histidyl-tRNA synthetase spacer. The epitopes were selected based on our previous docking studies. We then performed molecular docking of the polytope with the four bnAbs.
Results
The polytope bound precisely to the four bnAbs—B7, C8, A11, and C10. Moreover, the polytope had a higher affinity for the bnAbs compared to the DENV2 antigen. The polytope and A11 antibody complex had the lowest binding energy relative to complexes between the polytope and the other three antibodies assessed. The highest total number of hydrogen bonds was found in the polytope and B7 antibody complex. The hydrogen bond length in all the complexes ranged from 2.07 to 3.03 Å, implying that hydrogen bonds stabilized the complexes.
Conclusion
The developed polytope interacted with four different bnAbs that recognize the four serotypes of dengue virus. The results of this study suggest that this polytope warrants further development for use in a broad-spectrum vaccine against dengue virus.
Currently, people prefer to use herbal treatment because it is considered relatively cheaper, efficient, and smaller in its side effects compared to synthetic drugs. However, it does not mean that herbal medicine has no adverse side effects if it is used in less precise. Some plants that have properties as antifertility, as well as hepatoprotective, are pegagan (Centella asiatica) and beluntas (Pluchea indica). This study aimed to find a combination dosage of pegagan and beluntas extract that was safe to the liver. The research design used a completely randomized design with six treatments and four replications. The leaf extract of pegagan and beluntas with doses of 0, 25+25, 50+50, 75+75, 125+125, and 200+200 mg/kg BW was administered to 24 female Wistar strains. The data of glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), and the level of liver histological damage were analyzed using ANOVA (α 5%) and followed by DMRT (α 5%). The results revealed that the administration of the leaf extract of pegagan and beluntas up to doses of 200+200 mg/kg BW did not affect GPT-GOT levels but began to show histological liver damage. In the conclusion, the use of a combination of pegagan and beluntas extract each up to a dose of 125+125 mg/kg BW was safe for the liver.
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