Predicting the possible biological markers as targeted therapy for dengue viral infections

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Arief Hidayatullah, Wira Eka Putra, Sustiprijatno, Galuh Wening Permatasari, Wa Ode Salma, Diana Widiastuti, Hendra Susanto, Dewi Ratih Tirto Sari, Febby Nurdiya Ningsih, Muhammad Fikri Heikal, Alyana Mahdavikia Rosyada Yusuf, Aliyya Suci Arizona

2021 Malaysian Journal of Biochemistry and Molecular Biology Vol. 24 Issue 1 Article Cited by 1 Quartile

Abstract

The incidence rate of dengue infections in Indonesia shows an upward trend every year. Recently, dengue infection treatment is still limited to symptom management and especially efforts to restore the body's immune system to fight the infection. There is still no immediate treatment and prevention mechanism for dengue infection. This study aimed to predict the possible targeted proteins in Dengue infection as biomarkers in further molecular assays in part of future drug development. In silico pathway analysis based on KEGG's database was performed to determine the target protein and visualized them into the 3D model through SWISS-Model and PyMOL. Each protein also tested for their interaction using STITCH based on two bioprocesses, namely the cytoplasmic pattern recognition receptor signaling and the innate immune response pathway. The analysis showed that three of the target proteins are RIG-I, MDA5, and MAVS, convincingly interacting in both pathways with very high predictions for specific actions value (0.800), compelling experimental/biochemical data (0.990 to 0.999), and a low false discovery rate value. RIG-I and MDA5 play an essential role as the viral RNA primary receptors in the early stages of DENV infection. Even by inhibiting these two proteins, it has a severe effect on the cytokine response. The MAVS protein was an essential antiviral protein that serves as a bridge between sensory proteins and responder proteins in innate immune cell mechanisms against DENV infections. © 2021 Malaysian Society for Biochemistry and Molecular Biology. All rights reserved.

Affiliations

Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, East Java, Indonesia; Department of Biotechnology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, East Java, Indonesia; Indonesian Center for Agricultural Biotechnology and Genetic Resources Research and Development, West Java, Indonesia; Indonesian Research Institute for Biotechnology and Bioindustry, Bogor, West Java, Indonesia; Department of Nutrition, Faculty of Public Health, Halu Oleo University, Indonesia; Departmentof Chemistry, Faculty of Mathematics and Natural Science, Universitas Pakuan, West Java, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Indonesia; Research Center of Smart Molecule of Natural Genetics Resources, Brawijaya University, Indonesia; Center of Pharmaceutical and Medical Technology, Agency for the Assessment and Application of Technology (BPPT), Serpong, South Tangerang, Indonesia