In Silico Investigation and Identification of Potential Therapeutic Phytocompounds Against Dengue Virus NS5 Methyltransferase

Dengue has become major global health threat, especially in tropical and subtropical region including Bangladesh. According to World Health Organization (WHO), 69483 cases of dengue were confirmed and 327 people were died in Bangladesh in 2023. In current year, it becomes more acute than previous indicating the emergence of exploring new effective drugs against dengue. So, in the current study, we have investigated potential phytochemicals against dengue virus. All flaviviruses undergo 5'-mRNA capping process protecting their RNA from the host; facilitate a successful replication and multiplication of the virus. The NS5 Methyltransferase protein of dengue virus is involved in this process of 5'-mRNA capping; blocking the activity of NS5 Methyltransferase is a promising target for antiviral drug development. To inhibit the the 5'-mRNA capping, initially we have selected 605 phytocompounds from four different plants, including Allium sativum, Curcuma longa, Camellia sinensis and Carica papaya. These phytocompounds were screened based on Lipinski’s violation and 180 phytocompounds were selected which followed no or one violation. These 180 phytocompounds were docked against NS5 methyltransferase protein and eight were selected based on their higher binding energy than the control (-7.648 kcal/mol) and Dehydrocarpaine I showed highest binding energy (-9.456 kcal/mol). Further, the selected phytocompounds again filtered based on their pharmacokinetic property, toxicity profile and interactions between the receptor-ligand complex. Four of them Dehydrocarpaine I, A1- Barrigenol, Theasapogenol B and Brassinolide compounds were performed molecular dynamic simulation for 100 nanoseconds at human body temperature 310K and three phytocompounds of them Dehydrocarpaine I, Theasapogenol B and Brassinolide were stable during molecular dynamic simulation. Finally, ligand-receptor binding free energy was also carried out where Theasapogenol B (-260.319 kJ/mol) showed highest binding free energy with the receptor. Also, the binding free energy of Brassinolide (-186.761 kJ/mol) is higher than the control (-181.076 kJ/mol) and both derived from Camellia sinensis plant. This computational approach identified these potential two lead-candidates can inhibit the dengue virus replication and multiplication, which serves as a preliminary guide for further in-vitro and in-vivo research for developing real drug.

• Supervision