IN SILICO DRUG DESIGNING STUDIES ON DENGUE VIRUS NS1 PROTEIN

Pharma Admission

Pharma courses

pharma admission

pharma courses

 

Docking of compound - B into NS1 protein:
From Table – 2 and Figure – 1, the docking studies of 11 compounds are performed for the target envelope protein. In our results on the binding conformation modes of compounds with envelope protein, compound - B shows higher affinity with the NS1 protein. In examining the binding interaction and position of the compound B with NS1 protein ligand binding site predicted by your docking procedure, it is found that two strong hydrogen bonds are formed, one with branched chain residue Pro 224 having -3.3 kcal/mol as its bond energy and another hydrogen bond is formed with the branched chains of Lys 245 with – 3.5 kcal/mol as bond energy.  A close-up view of binding mode of compound – B with envelope protein is shown in Fig.3.

Fig. 3: A close-up view of binding mode of compound – B with NS1 protein

Docking of compound - C into NS1 protein:
From Table – 2 and Figure – 1, the docking studies of 11 compounds are performed for the target envelope protein. In our results on the binding conformation modes of compounds with envelope protein, compound - C shows higher affinity with the NS1 protein. In examining the binding interaction and position of the compound C with NS1 protein ligand binding site predicted by your docking procedure, it is found that three strong hydrogen bonds are formed, one with branched chain residue Lys 227 having -4.7 kcal/mol as its bond energy, one with two with the side chain of Trp 232 and the third one with the side chain of Lys 206, both having -3.5 kcal/mol as bond energy.  A close-up view of binding mode of compound – C with envelope protein is shown in Fig.4.

Fig. 4: A close-up view of binding mode of compound – C with NS1 protein

CONCLUSION: Our molecular docking studies explored the possible binding modes of 11 compounds that are present in dragon fruit seed with envelope protein. It revealed that all the 11 compounds show minimum affinity with envelope protein. Especially the compound A (7,10,13-hexadecatrienoic acid ), compound B (9,12,15-octadecatrienoic acid) and compound C (9,12-octadecadienoic acid) shows best result as compared to other compounds. On comparing the binding energy and the binding site residues, we found that all compounds differ either in their binding modes or with the binding site residues for hydrogen bond formation. The conclusion drawn from our virtual screening and docking result was that the Compound A, Compound B and Compound C have highest binding affinity with the NS1 Protein. Though, there are many reports on the in vitro analysis of these compounds and its antioxidant properties, but there are no in silico studies that predict the binding and active regions especially with NS1 protein. Our study is probably the first such attempt to predict the binding site. However, validation of our results through in vivo and in vitro experiments and also with animal models will enlighten hope for the future development of more potent drugs for the treating Dengue.

CONCLUSION:
Our molecular docking studies explored the possible binding modes of 11 compounds that are present in dragon fruit seed with envelope protein. It revealed that all the 11 compounds show minimum affinity with envelope protein. Especially the compound A (7,10,13-hexadecatrienoic acid ), compound B (9,12,15-octadecatrienoic acid) and compound C (9,12-octadecadienoic acid) shows best result as compared to other compounds. On comparing the binding energy and the binding site residues, we found that all compounds differ either in their binding modes or with the binding site residues for hydrogen bond formation. The conclusion drawn from our virtual screening and docking result was that the Compound A, Compound B and Compound C have highest binding affinity with the NS1 Protein. Though, there are many reports on the in vitro analysis of these compounds and its antioxidant properties, but there are no in silico studies that predict the binding and active regions especially with NS1 protein. Our study is probably the first such attempt to predict the binding site. However, validation of our results through in vivo and in vitro experiments and also with animal models will enlighten hope for the future development of more potent drugs for the treating Dengue.

REFERENCES:
1. Al-Khaboori SA, Balasubramanian S and Kumar KM (2015); In Silico Drug Designing on Human Protein Kinases Inhibitors; Int. J. Rec. Biotech.; 3 (4): 10-17
2. Ariffin AA, Bakar J, ChinPing T, Rahman RA, Karim R and Chiachun L (2009); Essential Fatty Acids of Pitaya (Dragon Fruit) Seed Oil. Food Chemistry; 114: 561-564.
3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN and Bourne PE (2000); The Protein Data Bank; Nucleic Acids Research; 28 (1): 235-242
4. Choo JC, Koh RY and Ling APK (2016); Medicinal Properties of Pitaya: A Review; Spatula DD; 6(2): 69-76.
5. Edeling MA, Diamond MS and Fremont DH (2014); Structural Basis of Flavivirus NS1 Assembly and Antibody Recognition; Proc. Natl. Acad. Sci.; 111: 4285-4290
6. Ferreira LG, Ricardo N, Oliva G and Andricopulo AD (2015); Molecular Docking and Structure-Based Drug Design Strategies; Molecules; 20: 13384-13421
7. Luo H, Cai Y, Liu Tao and Yang S (2014); Chemical Composition and in-vitro Evaluation of the Cytotoxic And Antioxidant Activities of Supercritical Carbon dioxide Extracts of Pitaya (Dragon Fruit) Peel; Chemistry Central Journal; 8:1
8. Malavige GN, Fernando S, Fernando DJ and Seneviratne SL (2004); Dengue Viral Infections; Postgrad Med J; 80: 588-601
9. Mehmood MA, Sehar U and Ahmad N (2014); Use of Bioinformatic Tools in Different Spheres of Life Sciences; Journal of Data Mining in Genomics & Proteomics; 5 (2): 1000158
10. Mejía HA, Ruiz SM, Montoya A and Sequeda CR (2013); In situ Morphological Characterization of Hylocereus spp. (Fam.: Cactaceae) Genotypes from Antioquia and Córdoba (Colombia); Rev. Fac. Nal. Agr. Medellín; 66(1): 6845-6854
11. Mello F R, Bernardo C, Dias C O, Züge L C B, Silveira J L M, Amante E R and Candido L M B (2014); Evaluation of the Chemical Characteristics and Rheological Behaviour of Pitaay (Hylocereus undatus) Peel; Fruits 2014; 69:381-390
12. Nurliyana R, Syed ZI, Mustapha SK, Aisyah MR and Kamarul RK (2010); Antioxidant Study of Pulp and Peels of Dragon Fruits: A Comparative Study. International Food Research Journal; 17:367-375
13. Perera R and Kuhn RJ (2008); Structural Proteomics of Dengue Virus; Curr Opin Microbiol; 11 (4): 369-377
14. Sushmitha HS, Roy CL, Gogoi D, Velagala RD, Nagarathna A, Balasubramanian S and Rajadurai M (2018); Phytochemical and Pharmacological Studies on Hylocereus undatus Seeds: An In Vitro Approach; World Journal of Pharmacological Research; 7 (14): 986-1006

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT editor-in-chief@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


 

Pages

FIND MORE ARTICLES