In vitro and in silico Anti-dengue activity of Supercritical extract of medicinal plants against Dengue serotype-2

2021 ◽  
pp. 5895-5902
Author(s):  
Sulochana Kaushik ◽  
Lalit Dar ◽  
Samander Kaushik ◽  
Ramesh Kumar ◽  
Devender Kumar ◽  
...  
Keyword(s):  
Dengue Virus ◽  
In Silico ◽  
Antiviral Drug ◽  
Docking Study ◽  
Tinospora Cordifolia ◽  
Ns1 Protein ◽  
Toxic Dose ◽  
Simplex Virus ◽  
Therapeutic Compounds

Dengue is transmitted by female Aedes mosquitoes. It has been reported that about 2.5 billion peoples are at the risk of dengue virus. Millions of cases of dengue virus occur worldwide each year. There is no antiviral drug available still. Hence, the researchers are in the search of new anti-dengue drugs from natural products. The present study is aimed to determine the anti-dengue activity of supercritical extracts of Andrographis paniculata, Berberis vulgaris, Carica papaya, Euphorbia hirta, Phyllanthus niruri and Tinospora cordifolia in vitro and in silico. The cell viability was evaluated in C6/36 cells line by using MTT assay using a microplate reader at 595 nm. The maximum non-toxic dose of C. papaya and B. vulgaris extracts were reported as 46.87µg/ml, 31.25µg/ml for A. paniculata, P. niruri and E. hirta and 23.43 µg/ml, for T. cordifolia. Further, the anti-dengue activity of plants extract was analyzed by real-time RT-PCR. 100 copies/ml of DENV-2 virus was used for the antiviral assay. A. paniculata supercritical extract showed complete inhibition against the dengue-2 virus at 40ºC temperature and 15Mpa pressure. The other plant extracts showed the inhibition in order of T. cordifolia (83.44%) > C. papaya (34.71%) > E. hirta (28.70%) whereas P. niruri and B. vulgaris failed to inhibit dengue virus. Andrographolide a major compound present in A. paniculata has been reported to have antiviral activity against hepatitis B, C virus, herpes simplex virus, influenza virus, chikungunya virus, dengue virus 2 and 4. Results of molecular docking showed that the interaction between andrographolide and NS1protein shows the maximum binding energy -7.30 Kcal/mol. The docking study was conducted to validate the result against the anti-dengue activity using dengue NS1 protein with andrographolide. It was concluded that A. paniculata could be a source for isolation of therapeutic compounds against the dengue-2 virus.

scholarly journals In vitro and in silico study to evaluate the effectiveness of quercitrin as antiviral drug to dengue virus

2019 ◽  
Author(s):  
Beti Ernawati Dewi ◽  
Edianti Ratningpoeti ◽  
Hidayati Desti ◽  
Marissa Angelina
Keyword(s):  
Dengue Virus ◽  
In Silico ◽  
Antiviral Drug ◽  
In Silico Study

Synthesis, SAR, In-Silico appraisal and Anti-Microbial Study of substituted 2-aminobenzothiazoles derivatives

2019 ◽  
Vol 15 ◽  
Author(s):  
Devidas G. Anuse ◽  
Suraj N. Mali ◽  
Bapu R. Thorat ◽  
Ramesh S. Yamgar ◽  
Hemchandra K. Chaudhari
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Gram Positive Bacteria ◽  
Ft Ir ◽  
In Silico Molecular Docking

Background: Antimicrobial resistance is major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. Methods: All synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. Results: The compounds 3d and 3h were showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in-silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. Conclusion: Our current study would definitely pave the new way towards designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

scholarly journals Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

scholarly journals Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

2021 ◽  
Vol 3 (1) ◽  
pp. 1-12
Author(s):  
Muhammad Mikail Athif Zhafir Asyura ◽  
Ahmad Fauzi ◽  
Fakhru Adlan Ayub
Keyword(s):  
Dengue Virus ◽  
Viral Replication ◽  
Dengue Fever ◽  
Immune Cells ◽  
Viral Protein ◽  
Viral Genome ◽  
Antiviral Drug ◽  
Ns1 Protein ◽  
Humoral Immune ◽  
Stimulation Of

Introduction: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Methods: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Conclusion: The review established promising results of using peptide-based intervention on NS1. Further in vivo and randomized controlled trials are advised to solidify the applicability and biosafety of the intervention    

NITD-688, a pan-serotype inhibitor of the dengue virus NS4B protein, shows favorable pharmacokinetics and efficacy in preclinical animal models

2021 ◽  
Vol 13 (579) ◽  
pp. eabb2181
Author(s):  
Stephanie A. Moquin ◽  
Oliver Simon ◽  
Ratna Karuna ◽  
Suresh B. Lakshminarayana ◽  
Fumiaki Yokokawa ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Pharmacokinetic Studies ◽  
Resistance Mutations ◽  
Binding Studies ◽  
Log Reduction ◽  
Elimination Half ◽  
Preclinical Animal Models

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to public health, yet no antiviral drug is available. We performed a high-throughput phenotypic screen using the Novartis compound library and identified candidate chemical inhibitors of DENV. This chemical series was optimized to improve properties such as anti-DENV potency and solubility. The lead compound, NITD-688, showed strong potency against all four serotypes of DENV and demonstrated excellent oral efficacy in infected AG129 mice. There was a 1.44-log reduction in viremia when mice were treated orally at 30 milligrams per kilogram twice daily for 3 days starting at the time of infection. NITD-688 treatment also resulted in a 1.16-log reduction in viremia when mice were treated 48 hours after infection. Selection of resistance mutations and binding studies with recombinant proteins indicated that the nonstructural protein 4B is the target of NITD-688. Pharmacokinetic studies in rats and dogs showed a long elimination half-life and good oral bioavailability. Extensive in vitro safety profiling along with exploratory rat and dog toxicology studies showed that NITD-688 was well tolerated after 7-day repeat dosing, demonstrating that NITD-688 may be a promising preclinical candidate for the treatment of dengue.

scholarly journals Illustrating and homology modeling the proteins of the Zika virus

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 275 ◽  
Author(s):  
Sean Ekins ◽  
John Liebler ◽  
Bruno J. Neves ◽  
Warren G. Lewis ◽  
Megan Coffee ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Crystal Structures ◽  
Zika Virus ◽  
Antiviral Drug ◽  
Homology Model ◽  
Model Quality ◽  
Glycoprotein E ◽  
Starting Point ◽  
Homology Models

The Zika virus (ZIKV) is a flavivirus of the familyFlaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it eitherin vitroorin vivo. ZIKV therefore epitomizes a neglected disease. Several suggested steps have been proposed which could be taken to initiate ZIKV antiviral drug discovery using both high throughput screens as well as structure-based design based on homology models for the key proteins. We now describe preliminary homology models created for NS5, FtsJ, NS4B, NS4A, HELICc, DEXDc, peptidase S7, NS2B, NS2A, NS1, E stem, glycoprotein M, propeptide, capsid and glycoprotein E using SWISS-MODEL. Eleven out of 15 models pass our model quality criteria for their further use. While a ZIKV glycoprotein E homology model was initially described in the immature conformation as a trimer, we now describe the mature dimer conformer which allowed the construction of an illustration of the complete virion. By comparing illustrations of ZIKV based on this new homology model and the dengue virus crystal structure we propose potential differences that could be exploited for antiviral and vaccine design. The prediction of sites for glycosylation on this protein may also be useful in this regard. While we await a cryo-EM structure of ZIKV and eventual crystal structures of the individual proteins, these homology models provide the community with a starting point for structure-based design of drugs and vaccines as well as a for computational virtual screening.

scholarly journals Drug-encapsulated carbon (DECON): A novel platform for enhanced drug delivery

2019 ◽  
Vol 5 (8) ◽  
pp. eaax0780 ◽  
Author(s):  
Tejabhiram Yadavalli ◽  
Joshua Ames ◽  
Alex Agelidis ◽  
Rahul Suryawanshi ◽  
Dinesh Jaishankar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Antiviral Drug ◽  
Cost Effective ◽  
Delivery Systems ◽  
Carbon Particles ◽  
Drug Conjugates ◽  
Carbon Structures ◽  
Simplex Virus

Current drug-delivery systems are designed primarily for parenteral applications and are either lipid or polymer drug conjugates. In our quest to inhibit herpes simplex virus infection via the compounds found in commonly used cosmetic products, we found that activated carbon particles inhibit infection and, in addition, substantially improve topical delivery and, hence, the efficacy of a common antiviral drug, acyclovir (ACV). Our in vitro studies demonstrate that highly porous carbon structures trapped virions, blocked infection and substantially improved efficacy when ACV was loaded onto them. Also, using murine models of corneal and genital herpes infections, we show that the topical use of drug-encapsulated carbon (DECON) reduced dosing frequency, shortened treatment duration, and exhibited higher therapeutic efficacy than currently approved topical or systemic antivirals alone. DECON is a nontoxic, cost-effective and nonimmunogenic alternative to current topical drug-delivery systems that is uniquely triggered for drug release by virus trapping.

Antiviral Potential of Spondias mombin L. Leaves Extract Against Herpes Simplex Virus Type-1 Replication Using In Vitro and In Silico Approaches

Planta Medica ◽  
2020 ◽  
Vol 86 (07) ◽  
pp. 505-515 ◽  
Author(s):  
Emerson M. da S. Siqueira ◽  
Tábata L. C. Lima ◽  
Laurita Boff ◽  
Sarah G. M. Lima ◽  
Estela M. G. Lourenço ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
Binding Mode ◽  
Surface Glycoprotein ◽  
Viral Attachment ◽  
Docking Simulations ◽  
Simplex Virus ◽  
Hsv 1

Abstract Spondias mobin leaves have been traditionally used for treating cold sores. The study investigated the mechanism of antiherpes action of S. mombin extract, fractions, and geraniin. Different concentrations of samples were used to evaluate the in vitro antiherpes activity (anti-HSV-1) in virucidal, post-infection, attachment, and penetration assays. The mechanism of action of geraniin was investigated considering the glycoproteins gB and gD of HSV-1 surface as potential molecular targets. Molecular docking simulations were carried out for both in order to determine the possible binding mode position of geraniin at the activity sites. The binding mode position was posteriorly optimized considering the flexibility of the glycoproteins. The chemical analysis of samples was performed by LC-MS and revealed the presence of 22 substances, which are hydrolysable tannins, O-glycosylated flavonoids, phenolic acids, and a carbohydrate. The extract, tannin-rich fraction and geraniin showed important in vitro virucidal activity through blocking viral attachment but showed no relevant inhibition of viral penetration. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin and the activity site of the glycoproteins, particularly the glycoprotein gB. In silico experiments indicated that geraniin is at least partially responsible for the anti-herpes activity through interaction with the viral surface glycoprotein gB, which is responsible for viral adsorption. These results highlight the therapeutic potential of S. mombin anti-herpes treatment and provides support for its traditional purposes. However, further studies are required to validate the antiviral activities in vivo, as well as efficacy in humans.

scholarly journals In vitro antiviral and immunomodulatory activity of arbidol and structurally related derivatives in herpes simplex virus type 1-infected human keratinocytes (HaCat)

2014 ◽  
Vol 63 (11) ◽  
pp. 1474-1483 ◽  
Author(s):  
Brunella Perfetto ◽  
Rosanna Filosa ◽  
Vincenza De Gregorio ◽  
Antonella Peduto ◽  
Annalisa La Gatta ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Immunomodulatory Activity ◽  
Simplex Virus

Arbidol (ARB) is an antiviral drug that has broad-spectrum activity against a number of viral infections. To date, there are no specific data regarding its effects against a herpesvirus. Here, the in vitro antiviral effect of ARB and structurally related derivatives were evaluated in HaCat cells on different steps of herpes simplex virus type 1 replication: adsorption, entry and post-entry. The simplified pyrrolidine analogue, 9a2, showed the best antiviral activity in vitro by reducing the plaque numbers by about 50 % instead of 42 % obtained with ARB at the same concentration. Furthermore, we have reported that all tested compounds evaluated for their immunomodulatory activity showed the ability to reduce the viral proteins VP16 and ICP27 and to modify the virus-induced cytokine expression, allowing the host cell a more efficient antiviral response.

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