Ethyl 4-(4-methylphenyl)-4-pentenoate from Vetiveria zizanioides Inhibits Dengue NS2B–NS3 Protease and Prevents Viral Assembly: A Computational Molecular Dynamics and Docking Study

Lavanya, P.; Ramaiah, Sudha; Anbarasu, Anand

doi:10.1007/s12013-016-0741-x

Cited by 11 publications

(4 citation statements)

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“…In spite of the importance of ENV and NS5 proteins for viral replication, well-conserved non-structural proteins such as NS1, NS3/NS2B have been also evaluated against phytochemicals reported in literature, and the evaluated interactions were favorable with scores ranging from − 6.71 to − 32.24 Kcal/mol according to MOE Dock tool [86] Similarly, NS3 was evaluated against the compounds derived from the medicinal plant Vetiveria zizanioides, and one compound showed favorable interactions according to the scores obtained with Surflex-dock, mediated by Hydrogen bonds with 2.72 Å being the lowest distance found mediating this interactions [87].…”

Section: Discussionmentioning

confidence: 99%

In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting

Trujillo-Correa

Quintero-Gil

Díaz-Castillo

et al. 2019

BMC Complement Altern Med

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BackgroundFor decades, bioprospecting has proven to be useful for the identification of compounds with pharmacological potential. Considering the great diversity of Colombian plants and the serious worldwide public health problem of dengue—a disease caused by the dengue virus (DENV)—in the present study, we evaluated the anti-DENV effects of 12 ethanolic extracts derived from plants collected in the Colombian Caribbean coast, and 5 fractions and 5 compounds derived from Psidium guajava.MethodsThe cytotoxicity and antiviral effect of 12 ethanolic extracts derived from plants collected in the Colombian Caribbean coast was evaluated in epithelial VERO cells. Five fractions were obtained by open column chromatography from the ethanolic extract with the highest selectivity index (SI) (derived from P. guajava, SI: 128.2). From the fraction with the highest selectivity (Pg-YP-I-22C, SI: 35.5), five compounds were identified by one- and two-dimensional nuclear magnetic resonance spectroscopy. The antiviral effect in vitro of the fractions and compounds was evaluated by different experimental strategies (Pre- and post-treatment) using non-toxic concentrations calculated by MTT method. The DENV inhibition was evaluated by plate focus assay. The results were analyzed by means of statistical analysis using Student’s t-test. Finally the antiviral effect in Silico was evaluated by molecular docking.ResultsIn vitro evaluation of these compounds showed that three of them (gallic acid, quercetin, and catechin) were promising antivirals as they inhibit the production of infectious viral particles via different experimental strategies, with the best antiviral being catechin (100% inhibition with a pre-treatment strategy and 91.8% with a post-treatment strategy). When testing the interactions of these compounds with the viral envelope protein in silico by docking, only naringin and hesperidin had better scores than the theoretical threshold of − 7.0 kcal/mol (− 8.0 kcal/mol and − 8.2 kcal/mol, respectively). All ligands tested except gallic acid showed higher affinity to the NS5 protein than the theoretical threshold.ConclusionEven though bioprospecting has recently been replaced by more targeted tools for identifying compounds with pharmacological potential, our results show it is still useful for this purpose. Additionally, combining in vitro and in silico evaluations allowed us to identify promising antivirals as well as their possible mechanisms of action.

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Section: Discussionmentioning

confidence: 99%

In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting

Trujillo-Correa

Quintero-Gil

Díaz-Castillo

et al. 2019

BMC Complement Altern Med

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“…Hence, to overcome such situation presently, available more resources, much faster, and advance scientific techniques need to be adopted and explored. Earlier, a number of studies have proposed various traditional and specific methods for the identification of different chemical entities and demonstrated their selective inhibition mechanism and inhibitory efficacy against NS3‐NS2B protease complex at different levels …”

Section: Introductionmentioning

confidence: 99%

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

Bhowmick

Alissa

Wabaidur

et al. 2020

J of Molecular Recognition

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Dengue infection is the most common arthropod-borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi-step virtual screening effort was conceived to screen out the entire "screening library" of the Asinex database. Initially, through "Lipinski rule of five" filtration criterion almost 0.6 million compounds were collected and docked with NS3-NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the "Virtual Screening Workflow" (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as -high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM-GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3-NS2B protein based on the investigation of molecular interactions map and protein-ligand fingerprint analyses. Different pharmacokinetics and drug-likeness parameters were also checked, which favour the potentiality of selected molecules for being drug-like candidates. The molecular dynamics (MD) simulation analyses of protein-ligand complexes were explained that NS3-NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM-GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3-NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3-NS2B protein subjected to experimental validation.

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“…The use of natural bioactive compounds has shown promising results by inhibiting the mainprotease from the literature [24][25][26] . All compounds used in the present study fulfilled Lipinski's rule of five.…”

Section: Results and Discussion Docking Bioactive Compounds Against M...mentioning

confidence: 99%

Individual and Synergistic Potential of Bioactive Compounds from Chrysopogon Zizanioides Against Main-Protease of SARSCov-2 using Computational Approach

Ragunathan

Ramakrishnan

Rajnish

2022

Biosci., Biotech. Res. Asia

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This study presents the anti-COVID potential of bioactive compounds from Chrysopogon zizanioides thorough in-silico molecular docking approach using AutoDock Vina software. As of our knowledge, the antiviral potential of all its bioactive compounds and their synergistic potentials against SARS-CoV-2 main-protease is not reported earlier. The results were promising with ß-Sitosterol (?G = -7.5 kcal/mol; Ki = 3.13 µM); Campesterol (?G = -7.4 kcal/mol; Ki = 3.71 µM); Stigmast-4-en-3-one (?G = -7.3 kcal/mol; Ki = 4.39 µM) forming noncovalent interactions with the amino acids in the active site of Mpro causing inhibition. The synergistic potential of compounds showed a significant sign of inhibition against Mpro with -7.9 kcal/mol with the sequential combination of ß-Sitosterol; Campesterol; Stigmast-4-en-3-one. The docking protocol validation was performed by re-docking and superimposing co-crystallized ligand, and interactions visualized using Discovery Studio 2020. Moreover, all the compounds satisfied Lipinski’s oral drug-likeliness properties to be used and oral drug. These bioactive compounds of Chrysopogon zizanioides showed low binding energies against SARS-CoV-2 Mpro which proved their anti-COVID potential. Thus, by incorporating Chrysopogon zizanioides for consumption in daily life, it is very likely that one can get rid of COVID-19.

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Ethyl 4-(4-methylphenyl)-4-pentenoate from Vetiveria zizanioides Inhibits Dengue NS2B–NS3 Protease and Prevents Viral Assembly: A Computational Molecular Dynamics and Docking Study

Cited by 11 publications

References 51 publications

In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting

In vitro and in silico anti-dengue activity of compounds obtained from Psidium guajava through bioprospecting

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

Individual and Synergistic Potential of Bioactive Compounds from Chrysopogon Zizanioides Against Main-Protease of SARSCov-2 using Computational Approach

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