Flavonoid Inhibitor of Dengue NS5 Polymerase: Dynamics & Binding Energy Analysis

Haider, N., Hasan, M. N., Onyango, J. & Asaduzzaman, M. Global landmark: 2023 marks the worst year for dengue cases with millions infected and thousands of deaths reported. IJID Reg. 13, 100459 (2024).

Google Scholar

Dengue – Global situation. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON518.

CDC. Current Dengue Outbreak. Dengue (2025).

Dengue worldwide overview. (2025).

Dengue and severe dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue.

2023 dengue outbreak in Bangladesh. Wikipedia (2025).

Dengue fever. Wikipedia (2025).

Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and Efficacy In Vivo | mBio. https://doi.org/10.1128/mbio.03097-22.

Chauhan, N., Gaur, K. K., Asuru, T. R. & Guchhait, P. Dengue virus: pathogenesis and potential for small molecule inhibitors. Biosci. Rep. 44, BSR20240134 (2024).

Google Scholar

Maddipati, V. C. et al. A Review on the Progress and Prospects of Dengue Drug Discovery Targeting NS5 RNA- Dependent RNA Polymerase. http://eurekaselect.comhttps://eurekaselect.com/article/106868.

Galiano, V., Garcia-Valtanen, P., Micol, V. & Encinar, J. A. Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach. DDDT 10, 3163–3181 (2016).

Google Scholar

Zong, K. et al. Design, synthesis, evaluation and molecular dynamics simulation of dengue virus NS5-RdRp inhibitors. Pharmaceuticals 16, 1625 (2023).

Google Scholar

Coulerie, P. et al. New inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as potential antiviral drugs for dengue treatment. Rec. Nat. Products 8, 286 (2014).

Google Scholar

Zandi, K. et al. Extract of Scutellaria baicalensis inhibits dengue virus replication. BMC Complement Altern Med 13, 91 (2013).

Google Scholar

Dhanasekaran Sivaraman, P. S. P. Exploration of Bioflavonoids Targeting Dengue Virus NS5 RNA-Dependent RNA Polymerase: In Silico Molecular Docking Approach. Journal of Applied Pharmaceutical Science 10: 016–022 (2020).

Berman, H. M. The protein data bank. Nucleic Acids Res. 28, 235–242 (2000).

Google Scholar

Lim, S. P. et al. Potent allosteric dengue virus NS5 polymerase inhibitors: mechanism of action and resistance profiling. PLoS Pathog 12, e1005737 (2016).

Google Scholar

Schrödinger Release 2023–1: Protein Preparation Workflow; Epik, Schrödinger, LLC, New York, NY, 2023; Impact, Schrödinger, LLC, New York, NY; Prime, Schrödinger, LLC, New York, NY, 2023.

Shivakumar, D., Harder, E., Damm, W., Friesner, R. A. & Sherman, W. Improving the prediction of absolute solvation free energies using the next generation OPLS force field. J. Chem. Theory Comput. 8, 2553–2558 (2012).

Google Scholar

Valdés-Jiménez, A. et al. PSC-db: A structured and searchable 3d-database for plant secondary compounds. Molecules 26, 1124 (2021).

Google Scholar

Zeng, X. et al. NPASS: Natural product activity and species source database for natural product research, discovery and tool development. Nucleic Acids Res. 46, D1217–D1222 (2018).

Google Scholar

Irwin, J. J. & Shoichet, B. K. ZINC–a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model 45, 177–182 (2005).

Google Scholar

Schrödinger Release 2023–1: LigPrep, Schrödinger, LLC, New York, NY, 2023.

Bajrai, L. H. et al. Assessing the inhibitory potential of anti-dengue compounds against Japanese encephalitis virus RNA dependent RNA polymerase: An in silico study. J. Biomol. Struct. Dyn. 42, 11844–11860 (2024).

Google Scholar

Glide. Schrödinger https://www.schrodinger.com/platform/products/glide/.

Pettersen, E. F. et al. UCSF Chimera: A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

Google Scholar

What do all the Prime MM-GBSA energy properties mean? https://my.schrodinger.com/support/article/1875.

Homeyer, N. & Gohlke, H. Free energy calculations by the molecular mechanics poisson−boltzmann surface area method. Mol. Inf. 31, 114–122 (2012).

Google Scholar

Schrödinger Release 2023–1: Desmond Molecular Dynamics System, D. E. Shaw Research, New York, NY, 2024. Maestro-Desmond Interoperability Tools, Schrödinger, New York, NY, 2023.

Desmond | Schrödinger Life Science. Schrödinger https://www.schrodinger.com/platform/products/desmond/.

Price, D. J. & Brooks, C. L. A modified TIP3P water potential for simulation with Ewald summation. J. Chem. Phys. 121, 10096–10103 (2004).

Google Scholar

Harder, E. et al. OPLS3: A Force field providing broad coverage of drug-like small molecules and proteins. J. Chem. Theory Comput. 12, 281–296 (2016).

Google Scholar

LigPrep. Schrödinger https://www.schrodinger.com/platform/products/ligprep/.

(PDF) The Nose–Hoover thermostat. ResearchGate (2025).

Ke, Q., Gong, X., Liao, S., Duan, C. & Li, L. Effects of thermostats/barostats on physical properties of liquids by molecular dynamics simulations. J. Mol. Liq. 365, 120116 (2022).

Google Scholar

Principal Component Analysis – an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/principal-component-analysis.

Elhaik, E. Principal component analyses (PCA)-based findings in population genetic studies are highly biased and must be reevaluated. Sci Rep 12, 14683 (2022).

Google Scholar

Kagami, L. P., Das Neves, G. M., Timmers, L. F. S. M., Caceres, R. A. & Eifler-Lima, V. L. Geo-measures: A PyMOL plugin for protein structure ensembles analysis. Comput. Biol. Chem. 87, 107322 (2020).

Google Scholar

Papaleo, E., Mereghetti, P., Fantucci, P., Grandori, R. & De Gioia, L. Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: The myoglobin case. J. Mol. Graph. Model. 27, 889–899 (2009).

Google Scholar

Durham, E., Dorr, B., Woetzel, N., Staritzbichler, R. & Meiler, J. Solvent accessible surface area approximations for rapid and accurate protein structure prediction. J. Mol. Model 15, 1093–1108 (2009).

Google Scholar

Radius of Gyration: Know Definition, Formula, Applications here. Testbook https://testbook.com/physics/radius-of-gyration.

Sliwoski, G., Kothiwale, S., Meiler, J. & Lowe, E. W. Computational methods in drug discovery. Pharmacol. Rev. 66, 334–395 (2014).

Google Scholar

Huq, A. M. et al. Phenolic compounds of Theobroma cacao L. show potential against dengue RdRp protease enzyme inhibition by In-silico docking, DFT study, MD simulation and MMGBSA calculation. PLoS ONE 19(3), e0299238 (2024).

Google Scholar

Phunyal, A., Adhikari, A. & Subin, J. A. In silico exploration of potent flavonoids for dengue therapeutics. PLoS ONE 19, e0301747 (2024).

Google Scholar

Research Assistant – Bohrium | AI for Science with Global Scientists. https://www.bohrium.com/paper-details/discovering-potential-inhibitors-against-dengue-virus-ns5-rna-dependent-rna-polymerase-from-local-vegetables-a-comparative-computational-study/1136669465862209550-130061?utm_source=chatgpt.com.