Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease

Mahamudul Hasan; Md Mukthar Mia; Shahab Uddin Munna; Md Mowdudul Hasan Talha; Kanon Das

doi:10.1016/j.imu.2022.100932

Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease

Inform Med Unlocked. 2022:30:100932. doi: 10.1016/j.imu.2022.100932. Epub 2022 Mar 26.

Authors

Mahamudul Hasan¹, Md Mukthar Mia^{2

1}, Shahab Uddin Munna¹, Md Mowdudul Hasan Talha^{1

3}, Kanon Das^{1

3}

Affiliations

¹ Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.
² Department of Poultry Science, Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.
³ Department of Pharmacology and Toxicology, Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet, 3100, Bangladesh.

Abstract

Dengue fever is a virus spread by mosquitoes that has no effective treatment or vaccination. Several dengue cases combined with the current COVID-19 pandemic, exacerbates this problem. Two proteins, NS5 methyltransferase and NS2B/NS3 primary protease complexes, are crucial for dengue viral replication and are the target sites for antiviral development. Thus, this study screened published literature and identified 162 marine fungus-derived compounds with active bioavailability. Following Lipinski's rules and antiviral property prediction, 41 compounds were selected for docking with NS5 methyltransferase and NS2B/NS3 protease (PDB ID: 6IZZ and 2FOM) to evaluate compounds that could stop the action of dengue viral protein complexes. To find the best candidates, computational ADME, toxicity, and drug target prediction were performed to estimate the potential of the multi-targeting fungal-derived natural compounds. Analyzing the result from 41 compounds, Chevalone E (-13.5 kcal/mol), Sterolic acid (-10.3 kcal/mol) showed higher binding energy against dengue NS2B/NS3 protease; meanwhile, Chevalone E (-12.0 kcal/mol), Brevione K (-7.4 kcal/mol), had greater binding affinity against NS5 methyltransferase. Consequently, this study suggests that Chevalone E is an effective inhibitor of NS5 methyltransferase and NS2B/NS3 protease. Ligand-based virtual screening from DrugBank was utilized to predict biologically active small compounds against dengue virus NS2B/NS3 major protease and NS5 methyltransferase. Both licensed medications, estramustine (DB01196) and quinestrol (DB04575), were found to be similar to Chevalone E, with prediction scores of 0.818 and 0.856, respectively. In addition, cholic acid (DB02659), acitretin (DB00459), and mupirocin (DB00410) are similar to Sterolic acid, zidovudine (DB00495), imipenem (DB01598), and nadolol (DB01203) are similar to Brocazine A, and budesonide (DB01222) and colchicine (DB01394) are related to Brevione K. These findings suggest that these could be feasible dengue virus treatment options, meaning that more research is needed.

Keywords: Dengue virus; Drug prediction; Marine-derived compounds; Molecular docking; NS2B/NS3 protease; NS5 methyltransferase; Target-prediction.