Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease

Qamar, Muhammad Tahir ul; Mumtaz, Arooj; Ashfaq, Usman Ali; Azhar, Samia; Fatima, Tabeer; Hassan, Muhammad Radzi Abu; Hussain, Syed Sajid; Akram, Waheed; Idrees, Sobia

doi:10.6026/97320630010115

Cited by 22 publications

(15 citation statements)

References 12 publications

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“…Docking analysis provided various designs that were scored to decide ideal restricting modes. We found very high scores of docking than previously reported data [ 26 ]. Docking analysis contributed towards basic idea and binding energy values for each ligand.…”

Section: Discussioncontrasting

confidence: 61%

Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

et al. 2018

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BackgroundDue to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Therefore, the NS2B-NS3 is a well-characterized target for designing antiviral drug.ResultsIn this study docking analysis was performed with active site of dengue NS2B-NS3 protein with selected plant flavonoids. More than 100 flavonoids were used for docking analysis. On the basis of docking results 10 flavonoids might be considered as the best inhibitors of NS2B-NS3 protein. The interaction studies showed resilient interactions between ligand and receptor atoms. Furthermore, QSAR and SAR studies were conducted on the basis of NS2B-NS3 protease complex docking results. The value of correlation coefficient (r) 0.95 shows that there was a good correlation between flavonoid structures and selected properties.ConclusionWe hereby suggest that plant flavonoids could be used as potent inhibitors of dengue NS2B-NS3 protein and can be used as antiviral agents against dengue virus. Out of more than hundred plant flavonoids, ten flavonoid structures are presented in this study. On the basis of best docking results, QSAR and SAR studies were performed. These flavonoids can directly work as anti-dengue drug or with little modifications in their structures.

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Section: Discussioncontrasting

confidence: 61%

Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

et al. 2018

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“…The analysis has revealed 24 compounds that docked strongly to dengue virus NS2B-NS3 protease ( E dock < -130 kJ/mol) but not as strongly with mammalian trypsin, 21 compounds that docked strongly to the ATP binding site of DENV NS3 helicase ( E dock < -140 kJ/mol), 13 compounds that docked strongly to DENV methyltransferase ( E dock < -130 kJ/mol) but not as strongly with human RNA methyltransferase, 8 phytochemicals that showed notable docking to DENV RNA-dependent RNA polymerase, and 32 compounds that showed excellent docking properties with the hydrophobic pore of DENV envelope protein. The results of this study mirror previous docking studies that showed polyphenolic phytochemicals to be excellent docking ligands to dengue protein targets [42, 43, 46, 61]. These results and the current study underscore the importance of natural products from higher plants in drug discovery and may provide potential avenues for development of chemotherapeutic agents for the treatment of dengue fever.…”

Section: Discussionsupporting

confidence: 88%

An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever

Powers¹,

Setzer

2016

CCHTS

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A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets.

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“…and C 29 H 25 N 3 O 4 S, CID 54710332; Figure 1) and Ile165 were also reported by Salaemae et al [63] as determinants of binding with the substrate in the active site of the dengue virus NS3 protease, as was also noted by other authors [35,64,65].…”

supporting

confidence: 78%

Discovery of antiviral molecules for dengue: In silico search and biological evaluation

Cabarcas-Montalvo

Maldonado-Rojas

Montes-Grajales

et al. 2016

European Journal of Medicinal Chemistry

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Background: Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation.Methods: NS2B/NS3 protease complex structural information was employed to find small molecules that are capable of inhibiting the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrate and the complex NS2B/NS3 obtained by recombinant DNA techniques, for testing the activity against dengue virus replication, HepG2 cells infected with dengue virus serotype 2 were used. Results: A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that were capable of inhibiting this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. Conclusions: Chemicals CID54681617, CID54692801 and CID54715399 were strong inhibitors of NS2B/NS3, with IC 50 values (µM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9 %, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. General significance: This discovery opens new possibilities for obtaining drug candidates against Dengue virus.

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Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease

Cited by 22 publications

References 12 publications

Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever

Discovery of antiviral molecules for dengue: In silico search and biological evaluation

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