Anti-dengue Agents Research Articles

In Silico-Based Identification of Natural Inhibitors from Traditionally Used Medicinal Plants that can Inhibit Dengue Infection.

Dengue fever (DF) is an endemic disease that has become a public health concern around the globe. The NS3 protease-helicase enzyme is an important target for the development of antiviral drugs against DENV (dengue virus) due to its impact on viral replication. Inhibition of the activity of the NS3 protease-helicase enzyme complex significantly inhibits the infection associated with DENV. Unfortunately, there are no scientifically approved antiviral drugs for its prevention. However, this study has been developed to find natural bioactive molecules that can block the activity of the NS3 protease-helicase enzyme complex associated with DENV infection through molecular docking, MM-GBSA (molecular mechanics-generalized born surface area), and molecular dynamics (MD) simulations. Three hundred forty-two (342) compounds selected from twenty traditional medicinal plants were retrieved and screened against the NS3 protease-helicase protein by molecular docking and MM-GBSA studies, where the top six phytochemicals have been identified based on binding affinities. The six compounds were then subjected to pharmacokinetics and toxicity analysis, and we conducted molecular dynamics simulations on three protein-ligand complexes to validate their stability. Through computational analysis, this study revealed the potential of the two selected natural bioactive inhibitors (CID-440015 and CID-7424) as novel anti-dengue agents.

Evaluation for Antiviral Potential of Ficus deltoidea Against Dengue Virus Type-2

Dengue is one of the most widespread arthropod-borne viral diseases that cause negative impact globally. Presently, no effective drug is available to safeguard people against dengue. Ficus deltoidea is Malaysia's famous traditional herb belonging to Moraceae family due to its pharmacological potential. F. deltoidea leaves (FDL) were extracted with n-hexane, ethyl acetate and methanol. Cell cytotoxicity study using MTT assay measuring the formazan absorbance was conducted to determine maximum non-toxic concentration on Vero cells. The antiviral activities of various concentrations of FDL extracts were assessed using virus reduction neutralisation tests against dengue virus type 2. The CC20 value of n-hexane, ethyl acetate and methanol FDL extracts were 2.99 ± 0.31, 22.15 ± 2.39, and 25.22 ± 0.42 µg/mL, respectively. Methanol FDL extract at maximum non-toxic concentration exerted strongest direct extracellular virucidal effect against DENV-2. In cell protection assay, ethyl acetate FDL extract achieved highest reduction in viral infectivity (98.17%), whereas n-hexane FDL extract showed strongest inhibition in DENV-2 viral replication in post-infection assay. Methanol FDL extract showed highest selectivity index value in direct virus inhibition, cell protection and post-infection assay. Conclusively, FDL extracts, especially methanol FDL showed potential antiviral activity against DENV-2, thus considered as promising anti-dengue agent.

Computational studies demonstrating dithymoquinone of Nigella sativa as a potential anti-dengue agent: Short review

Dengue is acute tropical infectious illness, which is spread by mosquitoes, has presented a significant threat to public health worldwide. Unfortunately, there are no drugs that have been clinically proven to be effective at treating or preventing dengue. The development of some drugs is significantly hampered by our incomplete understanding of dengue pathogenesis. This short review provides a brief description of potential action against DENV of dithymoquinone to develop an anti-DENV inhibitor. In-vitro, in-vivo and clinical trials are required to establish the effectiveness and safety of dithymoquinone as an anti-dengue therapy, even though computational studies have demonstrated antiviral activity against DENV.

Synthesis and biological activity of imidazole phenazine derivatives as potential inhibitors for NS2B-NS3 dengue protease

A series of new imidazole-phenazine derivatives were synthesized via a two-step process. The condensation of 2,3-diaminophenazine and benzaldehyde derivatives proceeds with intermediate formation of an aniline Schiff base, which undergoes subsequent cyclodehydrogenation in situ. The structures of the synthesized compounds were characterized by 1D and 2D NMR, FTIR and HRMS. A total of thirteen imidazole phenazine derivatives were synthesized and validated for their inhibitory activity as anti-dengue agents by an in vitro DENV2 NS2B-NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Two para-substituted imidazole phenazines, 3e and 3k, were found to be promising lead molecules for novel NS2B-NS3 protease inhibitors with IC50 of 54.8 μM and 71.9 μM, respectively, compared to quercetin as a control (IC50 104.8 μM). The in silico study was performed using AutoDock Vina to identify the binding energy and conformation of 3e and 3k with the active site of the DENV2 NS2B-NS3 protease Wichapong model. The results indicate better binding properties of 3e and 3k with calculated binding energies of −8.5 and −8.4 kcal mol−1, respectively, compared to the binding energy of quercetin of −7.2 kcal mol−1, which corroborates well with the experimental observations.

Investigating Lycotoxin-An1a (An1a), a defense antiviral peptide from Alopecosa nagpag venom as prospective anti-dengue agent against DENV-2 NS2B-NS3 protease

Dengue fever is a global health concern with no effective therapy. Screening synthetic chemicals, animal-originated compounds, and phytocompounds against Dengue virus (DENV) targets has failed to find dengue antivirals. The current study examines animal drugs as antagonists against NS2B-NS3Pro, one of DENV's most promising therapeutic targets for dengue fever. Antiviral-Lycotoxin-An1a (An1a), a defence antiviral peptide isolated from the venom of Alopecosa nagpag, a toxic spider. Based on prior in vitro research, it was discovered that the venom peptide suppresses the action of DENV-2 NS2B-NS3Pro. An1a peptide with NS2B-NS3Pro wild type (WT) and two mutants (H51N and S135A) was tested for anti-dengue characteristics using in silico analysis. The WT NS2B-NS3Pro has a catalytic triad of His51, Asp75, and Ser135 in the active site, but the mutants have N51 instead of His51 and Ala135 instead of Ser135. The dynamic sites of the three proteases (WT, H51N, S135A) and the peptide toxin (An1a) were taken into account to achieve molecular docking of An1a with WT NS2B-NS3Pro in conjunction with H51N and S135A. Cluspro-2 performs rigid-flexible docking to predict peptide binding affinity, effectiveness, and inhibitory consistency. Since the ligand had a higher binding affinity, docking score, and molecular interaction network, MD simulations and MM-GBSA free energy calculations were used to investigate the stability of the three protein-peptide complexes. The computer-aided screening and manufacture of spider venom-based anti-dengue medicines yielded intriguing results in the preliminary studies. This study is significant in defining the ideal therapeutic candidate against dengue infections.

Selected phytochemicals of Momordica charantia L. as potential anti-DENV-2 through the docking, DFT and molecular dynamic simulation

Dengue fever is now one of the major global health concerns particularly for tropical and sub-tropical countries. However, there has been no FDA approved medication to treat dengue fever. Researchers are looking into DENV NS5 RdRp protease as a potential therapeutic target for discovering effective anti-dengue agents. The aim of this study to discover dengue virus inhibitor from a set of five compounds from Momordica charantia L. using a series of in-silico approaches. The compounds were docked into the active area of the DENV-2 NS5 RdRp protease to obtain the hit compounds. The successful compounds underwent additional testing for a study on drug-likeness similarity. Our study obtained Momordicoside-I as a lead compound which was further exposed to the Cytochrome P450 (CYP450) toxicity analysis to determine the toxicity based on docking scores and drug-likeness studies. Moreover, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties for the lead compound. Moreover, the lead compound was next subjected to molecular dynamic simulation for 200 ns in order to confirm the stability of the docked complex and the binding posture discovered during docking experiment. Overall, the lead compound has demonstrated good medication like qualities, non-toxicity, and significant binding affinity towards the DENV-2 RdRp enzyme. Communicated by Ramaswamy H. Sarma

Evaluation of the inhibitory potency of anti-dengue phytocompounds against DENV-2 NS2B-NS3 protease: virtual screening, ADMET profiling and molecular dynamics simulation investigations

Dengue fever has been a worldwide concern, with 50–100 million new infections each year mainly due to five different serotypes of the Dengue virus (DENV). Designing a perfect anti-dengue agent that can inhibit all the serotypes by distinguishing antigenic differences is quite difficult. Previous anti-dengue researches have included chemical compounds screening against DENV enzymes. The ongoing analysis is meant for investigation of the plant-based compounds as antagonistic to DENV-2 focusing on the specific NS2B-NS3Pro target, a trypsin like serine protease that cuts the DENV polyprotein into separate proteins crucial for viral reproduction. Initially, a virtual library of more than 130 phytocompounds was prepared from previously published reports of plants with anti-dengue properties, which were then virtually screened and shortlisted against the WT, H51N and S135A mutant of DENV-2 NS2B-NS3Pro. The three top-most compounds were viewed as Gallocatechin (GAL), Flavokawain-C (FLV), and Isorhamnetin (ISO) showing docking scores of −5.8, −5.7, −5.7 kcal/mol for WT, −7.5, −6.8, −7.6 kcal/mol for the H51N, and −6.9, −6.5, −6.1 kcal/mol for the S135A mutant protease, respectively. 100 ns long MD simulations and MM-GBSA based free energy calculations were performed on the NS2B-NS3Pro complexes to witness the relative binding affinity of the compounds and favourable molecular interactions network. A comprehensive analysis of the study reveals some promising outcomes with ISO as the topmost compound with favourable pharmacokinetic properties for the WT and mutants (H51N and S135A) as well, suggesting as a novel anti-NS2B-NS3Pro agent with better adapting characters in both the mutants. Communicated by Ramaswamy H. Sarma

A Genome-Wide RNAi Screen Reveals Common Host-Virus Gene Signatures: Implication for Dengue Antiviral Drug Discovery.

Dengue is the most common mosquito-borne viral disease that in recent years has become a major international public health concern. Dengue is a tropical neglected disease with increasing global incidences, affecting millions of people worldwide, and without the availability of specific treatments to combat it. The identification of host-target genes essential for the virus life cycle, for which effective modulators may already exist, would provide an alternative path to a rapid drug development of the much needed antidengue agents. For this purpose, we performed the first genome-wide RNAi screen, combining two high-content readouts for dengue virus infection (DENV E infection intensity) and host cell toxicity (host cell stained nuclei), against an arrayed lentiviral-based short hairpin RNA library covering 16,000 genes with a redundancy of at least 5 hairpins per gene. The screen identified 1924 gene candidates in total; of which, 1730 gene candidates abrogated dengue infection, whereas 194 gene candidates were found to enhance its infectivity in HEK293 cells. A first pass clustering analysis of hits revealed a well-orchestrated gene-network dependency on host cell homeostasis and physiology triggering distinct cellular pathways for infectivity, replication, trafficking, and egress; a second analysis revealed a comprehensive gene signature of 331 genes common to hits identified in 28 published RNAi host-viral interaction screens. Taken together, our findings provide novel antiviral molecular targets with the potential for drug discovery and development.

A Review on Unleashing the Potentials of Natural Products in Managing Dengue

Background/Aims: Dengue virus (DENV) spreads widely in many tropical and sub-tropical countries by Aedes sp. In recent decades, dengue has been alarmingly on the rise and affects approximately half of the world population. The current dengue treatments are still mainly supportive without any approved vaccines or effective anti-dengue drugs. This leads to an urgency to seek alternative solutions in reducing dengue morbidity and mortality. Methods: A total of 94 articles describing in vitro and in vivo studies were screened and selected through curated databases. The selected articles underpinned the potentials of natural products as alternative anti-dengue compounds. Results: Those compounds have been employed as larvicide, mosquitocide, mosquito repellents, agents in sticky traps and non-specific interventions for dengue. In this review, their direct and indirect effects on dengue virus replication and dengue diseases were deliberated. Inteestingly, the majority of them demonstrated remarkable anti-inflammatory effects on dengue diseases. Several phytochemical contents such as luteolin, coumarins and geraniin were shown to inhibit DENV replication in vitro. Conclusion: Natural product-based anti-dengue agents are believed to be less costly, easy to derive, biologically effective and less toxic. This review, therefore, aims to provide current updates and insights on the benefits of natural products in preventing, managing and treating dengue.

Design, synthesis, in vitro, in silico, and SAR studies of flavone analogs towards anti-dengue activity

Flavone has recently been proved as a promising scaffold for the development of a novel drug against dengue fever, one of the major health threats globally. However, the structure–activity relationship study of flavones on the anti-dengue activity remains mostly limited to the natural-occuring analogs. Herein, 27 flavone analogs were successfully synthesized, of which 5 analogs (5e, 5h, 5o, 5q, and 5r) were novel. In total, 33 analogs bearing a diverse range of substituents were evaluated for their efficacy against DENV2-infected LLC/MK2 cells. The introduction of electron-withdrawing groups on ring B such as Br (5m) or NO2 (5n and 5q) enhanced the activity significantly. In particular, the tri-ester 5d and di-ester 5e exhibited low toxicity against normal cell, and exceptional DENV2 inhibition with the EC50 as low as 70 and 68 nM, respectively, which is over 300-fold more active compared to the original baicalein reference. The viral targets for these potent flavone analogs were predicted to be NS5 MTase and NS5 RdRp, as suggested by the likelihood ratios from the molecular docking study. The great binding interaction energy of 8-bromobaicalein (5f) confirms the anti-dengue activity at atomistic level. The physicochemical property of all the synthetic flavone analogs in this study were predicted to be within the acceptable range. Moreover, the QSAR model showed the strong correlation between the anti-dengue activity and the selected molecular descriptors. This study emphasizes the great potential of flavone as a core structure for further development as a novel anti-dengue agent in the future.

Targeting the DENV NS2B-NS3 protease with active antiviral phytocompounds: structure-based virtual screening, molecular docking and molecular dynamics simulation studies.

Dengue fever has been a global health concern. Mitigation is a challenging problem due to non-availability of workable treatments. The most difficult objective is to design a perfect anti-dengue agent capable of inhibiting infections caused by all four serotypes. Various tactics have been employed in the past to discover dengue antivirals, including screening of chemical compounds against dengue virus enzymes. The objective of the current study is to investigate phytocompounds as anti-dengue remedies that target the non-structural 2B and non-structural 3 protease (NS2B-NS3pro), a possible therapeutic target for dengue fever. Initially, 300 + antiviral phytocompounds were collected from Duke’s phytochemical and ethnobotanical database and 30 phytocompounds with anti-dengue properties were identified from previously reported studies, which were virtually screened against NS2B-NS3pro using molecular docking and toxicity evaluation. The top five most screened ligands were naringin, hesperidin, gossypol, maslinic acid and rhodiolin with binding affinities of − 8.7 kcal/mol, − 8.5 kcal/mol, − 8.5 kcal/mol, − 8.5 kcal/mol and − 8.1 kcal/mol, respectively. The finest docked compounds complexed with NS2B-NS3pro were subjected for molecular dynamics (MD) simulations and binding free energy estimations through molecular mechanics generalized born surface area–based calculations. The results of the study are intriguing in the context of computer-aided screening and the binding affinities of the phytocompounds, proposing maslinic acid (MAS) as a potent bioactive antiviral for the development of phytocompound-based anti-dengue agent.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00894-022-05355-w.

In Silico Elucidation of Potent Inhibitors from Natural Products for Nonstructural Proteins of Dengue Virus

Medicinal plants have been used from the beginning of human civilization against various health complications. Dengue virus (DENV) has emerged as one of the most widespread viruses in tropical and subtropical countries. Yet no clinically approved antiviral drug is available to combat DENV infection. Consequently, the search for novel antidengue agents from medicinal plants has assumed more insistence than in previous days. This study has focused on 31 potential antidengue molecules from secondary metabolites to examine their inhibitory activity against DENV nonstructural proteins through molecular docking and pharmacokinetics studies. In this research, the wet lab experiments were tested on a computational platform. Agathisflavone and pectolinarin are the top-scored inhibitors of DENV NS2B/NS3 protease and NS5 polymerase, respectively. Epigallocatechin gallate, Pinostrobin, Panduratin A, and Pectolinarin could be potential lead compounds against NS2B/NS3 protease, while acacetin-7-O-rutinoside against NS5 polymerase. Moreover, agathisflavone (LD50= 1430 mg/kg) and pectolinarin (LD50= 5000 mg/kg) exhibited less toxicity than nelfinavir (LD50= 600 mg/kg) and balapiravir (LD50 = 824 mg/kg), and the reference drugs. Further research on clinical trials is required to analyze the therapeutic efficacy of these metabolites to develop new potential drug candidates against different serotypes of DENV.

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus.

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.

Computational Atom-based Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Model for Predicting Anti-Dengue Agents

Dengue fever is a viral infection spread by the female mosquito Aedes aegypti. It is a virus spread by mosquitoes found all over the tropics with risk levels varying depending on rainfall, relative humidity, temperature and urbanization. There are no specific medications that can be used to treat the condition. The development of possible bioactive ligands to combat Dengue fever before it becomes a pandemic is a global priority. Few studies on building three-dimensional quantitative structure-activity relationship (3D QSAR) models for anti-dengue agents have been reported. Thus, we aimed at building a statistically validated atom-based 3D-QSAR model using bioactive ligands reported to possess significant anti-dengue properties. In this study, the Schrodinger PhaseTM atom-based 3D QSAR model was developed and was validated using known anti-dengue properties as ligand data. This model was also tested to see if there was a link between structural characteristics and anti-dengue activity of a series of 3-acyl-indole derivatives. The established 3D QSAR model has strong predictive capacity and is statistically significant [Model: R2 Training Set = 0.93, Q2 (R2 Test Set) = 0.72]. In addition, the pharmacophore characteristics essential for the reported anti-dengue properties were explored using combined effects contour maps (coloured contour maps: blue: positive potential and red: negative potential) of the model. In the pathway of anti-dengue drug development, the model could be included as a virtual screening method to predict novel hits.

A systematic review on phytochemicals for the treatment of dengue.

Dengue fever is prevalent in subtopic regions, producing mortality and morbidity worldwide, which have been of major concern to different governments and World Health Organization. The search of new anti-dengue agents from phytochemicals was assumed to be highly emergent in past. The phytochemicals have been used in wide distribution of vector ailments such as malaria. The demand of the phytochemicals is based on the medicines which are mostly considered to be safer, less harmful than synthetic drugs and nontoxic. This review mentions majorly about the phytochemicals potentially inhibiting dengue fever around the world. The phytochemicals have been isolated from different species, have potential for the treatment of dengue. Different crude extracts and essential oils obtained from different species showed a broad activity against different phytochemicals. The current studies showed that natural products represent a rich source of medicines toward the dengue fever. Furthermore, ethnobotanical surveys and laboratory investigation established identified natural plants species in the development of drug discovery to control the dengue fever.

Discovery of Dengue Virus Inhibitors.

To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.

Implementation of ensemble methods on QSAR Study of NS3 inhibitor activity as anti-dengue agent

ABSTRACT Dengue fever is a disease transmitted by infected mosquitoes. This disease spreads in several countries, especially those with a tropical climate. To date, there is no specific drug that can be used to treat dengue. Use of clinically investigated drugs, such as Balapiravir, is still not effective in inhibiting the activity of virus replication. The design of a drug candidate can be performed by using the non-structural protein 3 (NS3) as target. This study aimed to develop QSAR models to predict the inhibitory activity class of NS3 inhibitors. The classification was performed by using feature importance analysis for selecting the descriptors and three ensemble methods, i.e. random forest (RF), adaptive boosting (AdaBoost), and extremely randomized trees (ERT), for model design and prediction. Hyperparameter tuning was performed to improve the performance of the models. Based on the results, we found that model 9, developed from ERT produced the best performance with values of accuracy and AUC equal to 0.73 and 0.82, respectively. Use of y-scrambling method allowed us to confirm that the model was not related to the chance correlation.

Synthesis and Molecular Docking Study of 1-(3-Chloropropyl)-3,5-Bis((E)-4-Methoxybenzylidene)Piperidin-4-One as Dengue Virus Type 2 (DEN2) NS2B/NS3 Protease Inhibitor Candidate

Curcumin is a secondary metabolite compound that has diverse biological activities. However, it is easily hydrolyzed at physiological pH due to the presence of the β-diketone group. Therefore, the replacement of the β-diketone group with mono ketone is expected to overcome this issue. We hereby report the synthesis of mono ketone curcumin derivatives from piperidone by two-steps reactions. The synthesis of curcumin derivate 3 was carried out by Claisen-Schmidt condensation between 4-piperidone and 4-methoxybenzaldehyde using alkaline catalyst. The synthesized curcumin derivate 3 was then reacted with the 1-bromo-3-chloropropane to produce curcumin derivate 5, 1-(3-chloropropyl)-3.5-bis((E)-4-methoxybenzylidene)piperidin-4-one, with 72% yield. The calculated docking scores, the curcumin derivate 5 possessed a better affinity for receptors than the standard panduratin A. The curcumin derivate 5 has a lower docking score of -6.40 kcal/mol compared to panduratin A with value of -5.18 kcal/mol and also had strong binding interactions to DEN2 NS2B/NS3 protease. Thus, this compound is promising candidate as a new anti-dengue agent.

Anti-dengue potential of bioactive protein from exophytic bacteria that are symbiotic with brown algae Sargassum sp.

Symbiont bacteria of algae are bioactive metabolite sources with potential as medicinal raw materials. This study aims to find out the anti-dengue potential of a protein fraction isolated from Enterobacter agglomerans SB 5(1) as the symbiont of brown algae Sargassum binderi collected from Lae-Lae island, South Sulawesi. These extracellular and intracellular fractions were isolated by ammonium sulphate fractionation at saturation levels of 0-20 %, 20-40 %, 40-60 %, and 60-80 %. The protein was purified by dialysis method using cellophane bag. Toxicity was tested by BSLT method using shrimp larvae of Artemia salina, Leach. Cytotoxicity test against vero cells infected with dengue virus DEVN-2 was performed by MTT method. Study findings indicate that intracellular protein fraction from E. agglomerans SB 5(1), a symbiont of brown algae Sargassum binderi, showed the presence of bioactive protein having strong toxicity with LC50 of 48.67 µg/mL. Anti-dengue activity toward vero cells indicates inhibition percentage and CC50 value of 70% and 260.37 µg./mL, respectively, therefore it had no potential as anti-virus dengue agent. In future studies, it is recommended to perform hydrolysis of protein compound from symbiont bacteria of Sargassum sp. to explore other peptide compounds with more potential as anti-dengue agents.

Antiviral and therapeutic uses of medicinal plants and their derivatives against dengue viruses

Dengue fever (DF) is occurring worldwide, and it has emerged as a global health threat due to high mortality and morbidity, specifically in tropical and subtropical regions. The World Health Organization has deep concerned to this disease being a large section of population affected. Around 2.5 billion peoples are at risk of dengue virus (DENV). Over 100 countries including Europe and the United states are affected due to DENV. DF is the most widespread viral disease. There are four different serotypes (DENV-1 to DENV-4) of DENV but now discovered DENV-5 serotype also. DENV is transmitted from person to person by the bite of infected female Aedes aegypti and Aedes albopictus mosquito. Unfortunately, there are no effective approved anti-dengue agents and vaccine to treat viral infection. Researchers have paid attention toward medicinal plants in search of natural compounds which can be used as anti-dengue. Therefore, our focus is on the extract of medicinal plants which may be more effective, safer, and less toxic than synthetic drugs. In the present review paper, the brief description of 35 medicinal plants which possess anti-dengue activity has been documented along with their active components. This study will be helpful to establish that natural products may have good potential source of new anti-dengue compounds.