Molecular Docking and Molecular Dynamics Simulation of Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin Against Polymerase of Dengue Virus

Overview

Journal J Trop Med

Publisher Wiley

Specialty Tropical Medicine

Date 2022 Mar 31

PMID 35356488

Authors

Jaka Fajar Fatriansyah

Raihan Kenji Rizqillah

Muhammad Yusup Yandi

Affiliations

Soon will be listed here.

Abstract

Dengue fever is a disease spread by the DENV virus through mosquitoes. This disease is dangerous because there is no specific drug, vaccine, or antiviral against the DENV virus, insisting on drug discovery for dengue fever. RNA-dependent RNA polymerase (RdRp) enzyme in DENV can be a drug target because it has an important role in the virus replication process. In this research, in silico simulations were carried out on bioflavonoid compounds, namely, Fisetin, Galangin, Hesperetin, Hesperidin, Myricetin, and Naringenin with Quercetin as control ligand. QSAR analysis showed that all ligand has the probability to be antiviral and RNA synthesis inhibitor. Docking scores showed that Myricetin, Hesperidin, and Fisetin show strong performance while Hesperidin, Hesperetin, and Naringenin showed strong performance in MM/GBSA. Only Hesperidin showed strong performance in both scorings. Further investigation by ADMET analysis was done to investigate toxicology and pharmacological properties. Our molecular dynamics study through RMSD showed that even though Quercetin does not give good scoring values in both docking score and MM/GBSA, it has robust stable interaction to RdRp. The strong performance of Hesperidin was also validated by protein-ligand contact fraction in 5 ns. Overall, we observed that Hesperidin shows good potential as a DENV-3-RdRp inhibitor in par with Quercetin, although further in vitro study should be conducted.

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References

Falade V, Adelusi T, Adedotun I, Abdul-Hammed M, Lawal T, Agboluaje S . In silico investigation of saponins and tannins as potential inhibitors of SARS-CoV-2 main protease (M). In Silico Pharmacol. 2021; 9(1):9. PMC: 7786323. DOI: 10.1007/s40203-020-00071-w. View

Hemungkorn M, Thisyakorn U, Thisyakorn C . Dengue infection: a growing global health threat. Biosci Trends. 2010; 1(2):90-6. View

Patel S, Brooks 3rd C . CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations. J Comput Chem. 2003; 25(1):1-15. DOI: 10.1002/jcc.10355. View

Anusuya S, Gromiha M . Quercetin derivatives as non-nucleoside inhibitors for dengue polymerase: molecular docking, molecular dynamics simulation, and binding free energy calculation. J Biomol Struct Dyn. 2016; 35(13):2895-2909. DOI: 10.1080/07391102.2016.1234416. View

Picarazzi F, Vicenti I, Saladini F, Zazzi M, Mori M . Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge. Molecules. 2020; 25(23). PMC: 7730706. DOI: 10.3390/molecules25235695. View

Daina A, Michielin O, Zoete V . SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7:42717. PMC: 5335600. DOI: 10.1038/srep42717. View

Harapan H, Michie A, Yohan B, Shu P, Mudatsir M, Sasmono R . Dengue viruses circulating in Indonesia: A systematic review and phylogenetic analysis of data from five decades. Rev Med Virol. 2019; 29(4):e2037. DOI: 10.1002/rmv.2037. View

Leach A, Shoichet B, Peishoff C . Prediction of protein-ligand interactions. Docking and scoring: successes and gaps. J Med Chem. 2006; 49(20):5851-5. DOI: 10.1021/jm060999m. View

Ishikawa T, Hirano H, Saito H, Sano K, Ikegami Y, Yamaotsu N . Quantitative structure-activity relationship (QSAR) analysis to predict drug-drug interactions of ABC transporter ABCG2. Mini Rev Med Chem. 2012; 12(6):505-14. DOI: 10.2174/138955712800493825. View

10.

Chenafa H, Mesli F, Daoud I, Achiri R, Ghalem S, Neghra A . In silico design of enzyme α-amylase and α-glucosidase inhibitors using molecular docking, molecular dynamic, conceptual DFT investigation and pharmacophore modelling. J Biomol Struct Dyn. 2021; 40(14):6308-6329. DOI: 10.1080/07391102.2021.1882340. View

11.

Anusuya S, Gromiha M . Structural basis of flavonoids as dengue polymerase inhibitors: insights from QSAR and docking studies. J Biomol Struct Dyn. 2017; 37(1):104-115. DOI: 10.1080/07391102.2017.1419146. View

12.

Rajapakse S, Rodrigo C, Rajapakse A . Treatment of dengue fever. Infect Drug Resist. 2012; 5:103-12. PMC: 3411372. DOI: 10.2147/IDR.S22613. View

13.

Misini Ignjatovic M, Caldararu O, Dong G, Munoz-Gutierrez C, Adasme-Carreno F, Ryde U . Binding-affinity predictions of HSP90 in the D3R Grand Challenge 2015 with docking, MM/GBSA, QM/MM, and free-energy simulations. J Comput Aided Mol Des. 2016; 30(9):707-730. PMC: 5078160. DOI: 10.1007/s10822-016-9942-z. View

14.

Chen R, Vasilakis N . Dengue--quo tu et quo vadis?. Viruses. 2011; 3(9):1562-608. PMC: 3187692. DOI: 10.3390/v3091562. View

15.

Trott O, Olson A . AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2009; 31(2):455-61. PMC: 3041641. DOI: 10.1002/jcc.21334. View

16.

Friedman M . Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Mol Nutr Food Res. 2006; 51(1):116-34. PMC: 7168386. DOI: 10.1002/mnfr.200600173. View

17.

Tatura S, Denis D, Santoso M, Hayati R, Kepel B, Yohan B . Outbreak of severe dengue associated with DENV-3 in the city of Manado, North Sulawesi, Indonesia. Int J Infect Dis. 2021; 106:185-196. DOI: 10.1016/j.ijid.2021.03.065. View

18.

Zandi K, Teoh B, Sam S, Wong P, Mustafa M, AbuBakar S . Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J. 2011; 8:560. PMC: 3271998. DOI: 10.1186/1743-422X-8-560. View

19.

Cushnie T, Lamb A . Antimicrobial activity of flavonoids. Int J Antimicrob Agents. 2005; 26(5):343-56. PMC: 7127073. DOI: 10.1016/j.ijantimicag.2005.09.002. View

20.

Patlewicz G, Jeliazkova N, Safford R, Worth A, Aleksiev B . An evaluation of the implementation of the Cramer classification scheme in the Toxtree software. SAR QSAR Environ Res. 2008; 19(5-6):495-524. DOI: 10.1080/10629360802083871. View