scholarly journals Possible Anti-viral effects of Neem (Azadirachta indica) on Dengue virus

2020 ◽  
Author(s):  
Vikas B Rao ◽  
Kalidas Yeturu
Keyword(s):  
Dengue Virus ◽  
Small Molecules ◽  
Azadirachta Indica ◽  
Antiviral Drug ◽  
Experimental Studies ◽  
Major Health ◽  
Molecular Binding ◽  
Scientific Curiosity ◽  
Mosquito Breeding ◽  
Health Complications

Dengue virus (DENV) has become a major health threat worldwide accounting for 50-100 million infections every year and keeping 2.5 billion people at a risk of the infection. Seriousness of the viral infection can be attributed to its lethality when not treated in time and potential to cause health complications post infection. Currently there are only preventive strategies and development of vaccination is still in its infancy of research. It is therefore highly necessary to discover newer drugs and therapies for this deadly virus. In this paper we report important insights we have obtained through a computational analysis of small molecules of Neem (Azadirachta indica) against dengue viral proteins and its required proteins in human. Our study involves identification of the effect of specific small molecules of Neem on proteins of human and virus corresponding to different pathways using simulated molecular binding analyses. We report here Gedunin and Pongamol contained in naturally occurring Neem as potential drugs against the Dengue virus.Significance StatementWe report important ligands in Neem that have potential antiviral activity against Dengue. Our selection of Neem for testing for antiviral properties has been inspired from Ayurveda. Due to unhygienic living conditions that facilitate mosquito breeding, Dengue is a major threat in developing countries causing millions of deaths. Despite the severity of the infection, no specific antiviral drug is available. The results obtained, in terms of newer potential ligands against Dengue are significant as this provides a basis for experimentally verifying and extending the same to develop a cure.We hope that this study would would spur scientific curiosity and undertaking of further elaborate experimental studies.

Review on Dengue Virus Fusion/Entry Process and Their Inhibition by Small Bioactive Molecules

2020 ◽  
Vol 20 ◽  
Author(s):  
Podila Naresh ◽  
Shyam Sunder Pottabatula ◽  
Jubie Selvaraj
Keyword(s):  
Dengue Virus ◽  
Small Molecules ◽  
Conformational Changes ◽  
Yellow Fever Virus ◽  
Antiviral Drug ◽  
Bioactive Molecules ◽  
Fusion Process ◽  
Human Pathogens ◽  
Virus Infections ◽  
E Protein

: Many flavi viruses are noteworthy human pathogens which might be spread by means of mosquitoes and ticks. Despite the availability of vaccines for virus infections such as yellow fever virus, Japanese encephalitic virus, and tickborne encephalitis virus, still flavi virus like dengue is a serious life threatening disease globally. So far, there is no antiviral drug for dengue therapy. In order to address this scientific want, industry and scholarly community have been taking continuos measures to increase the anti flavivirus therapy. In the last two decades, active research is involved in inhibiting the fusion process of the virus entry. In this review, we have comprehensively given the present day expertise of usage of small molecules utilized as fusion inhibitors. We have enumerated the structure, fusion process of dengue virus E protein (DENV E) and amino acids involved during the fusion process. Special emphasis have been given for the small molecules that do conformational changes of DENV E protein viz. blocking the βOG pocket which is vital for fusion.

EFFECT OF KAGOCEL PREPARATION ON THE GENERATIVE FUNCTION OF EXPERIMENTAL ANIMALS AT ITS ADMINISTRATION IN THE INFANTILE PERIOD OF THEIR DEVELOPMENT

2017 ◽  
pp. 42-49
Author(s):  
T. A. Borovskaya ◽  
M. E. Poluektova ◽  
A. V. Vychuzhanina ◽  
V. A. Mashanova ◽  
Yu. A. Shchemerova
Keyword(s):  
Toxic Effect ◽  
Reproductive System ◽  
Safety Profile ◽  
Therapeutic Dose ◽  
Antiviral Drug ◽  
Experimental Studies ◽  
Reproductive Age ◽  
Pathological Changes ◽  
Pediatric Practice ◽  
Experimental Animals

In experimental studies on rats (males, females) at their infantile stage starting from 10 days, a potential delayed toxic effect of the antiviral drug Kagocel on the reproductive system was studied. The drug was administered for 12 days in a therapeutic dose and at a dose 10-fold higher than the therapeutic one. Reproductive safety was estimated after animals reached the reproductive age (2.5 months). It was found out that the drug, when administered in both doses, does not decrease the fertility of animals, does not induce morphological and pathological changes in the sex glands, and does not have toxic effect on the offspring. Obtained data characterize Kagocel as a preparation with a wide reproductive safety profile and show that it can be used in pediatric practice for infants.

scholarly journals Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1393
Author(s):  
Thanyaporn Dechtawewat ◽  
Sittiruk Roytrakul ◽  
Yodying Yingchutrakul ◽  
Sawanya Charoenlappanit ◽  
Bunpote Siridechadilok ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Site Directed Mutagenesis ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Multifunctional Protein ◽  
Nonstructural Protein 1 ◽  
Underlying Mechanisms

Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.

scholarly journals 4,7-Disubstituted 7H-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Small Molecules ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Structural Features ◽  
Molecular Target ◽  
Core Structure ◽  
Human Pathogens ◽  
Important Group

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

scholarly journals How Small Molecules Affect the Thermo-Oxidative Aging Mechanism of Polypropylene: A Reactive Molecular Dynamics Study

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1243
Author(s):  
Fan Zhang ◽  
Yufei Cao ◽  
Xuan Liu ◽  
Huan Xu ◽  
Diannan Lu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Acetic Acid ◽  
Small Molecules ◽  
Aging Process ◽  
Experimental Studies ◽  
Hydroxyl Group ◽  
Oxidative Aging ◽  
Reactive Molecular Dynamics ◽  
Aging Mechanism ◽  
Effects Of Temperature

Understanding the aging mechanism of polypropylene (PP) is fundamental for the fabrication and application of PP-based materials. In this paper, we present our study in which we first used reactive molecular dynamics (RMD) simulations to explore the thermo-oxidative aging of PP in the presence of acetic acid or acetone. We studied the effects of temperature and oxygen on the aging process and discussed the formation pathways of typical small molecule products (H2, CO, CO2, CH4, C2H4, and C2H6). The effect of two infection agents, acetic acid and acetone, on the aging reaction was analyzed emphatically. The simulation results showed that acetone has a weak impact on accelerating the aging process, while acetic acid has a significant effect, consistent with previous experimental studies. By tracking the simulation trajectories, both acetic acid and acetone produced small active free radicals to further react with other fragment products, thus accelerating the aging process. The first reaction step of acetic acid is often the shedding of the H atom on the hydroxyl group, while the reaction of acetone is often the shedding of the H atom or the methyl. The latter requires higher energy at lower temperatures. This is why the acceleration effect of acetone for the thermo-oxidative aging of PP was not so significant compared to acetic acid in the experimental temperature (383.15 K).

Localized Collection of Airborne Analytes: A Transport Driven Approach to Improve the Response Time of Existing Gas Sensor Designs including SERS based Detection of Small Molecules

2015 ◽  
Vol 1746 ◽  
Author(s):  
Jun Fang ◽  
Se-Chul Park ◽  
Leslie Schlag ◽  
Thomas Stauden ◽  
Joerg Pezoldt ◽  
...  
Keyword(s):  
Response Time ◽  
Small Molecules ◽  
Gas Sensor ◽  
Recent Trend ◽  
Active Area ◽  
Analyte Concentration ◽  
Analyte Molecule ◽  
Collection Rate ◽  
Molecular Binding ◽  
Increased Sensitivity

ABSTRACTThe detection of single molecular binding events has been a recent trend in sensor research introducing various sensor designs where the active sensing elements are nanoscopic in size. Currently, diffusion-only-transport is often used and it becomes increasingly unlikely for an analyte molecule to “find” and interact with sensing structures where the active area is shrunk in size, trading an increased sensitivity with a long response time. This report introduces electrodynamic nanolens based analyte concentration concepts to transport airborne analytes to nanoscopic sensing points to improve the response time of existing gas sensor designs. In all cases we find that the collection rate is several orders of magnitudes higher than in the case where the collection is driven by diffusion.

scholarly journals APPLICATION OF NANOTECHNOLOGY IN FOOD TECHNOLOGY AND TARGETED DRUG THERAPY FOR PREVENTION OF OBESITY: AN OVERVIEW

2016 ◽  
Vol 4 (1) ◽  
pp. 7 ◽  
Author(s):  
Jyotibala Banjare
Keyword(s):  
Drug Therapy ◽  
Medical Condition ◽  
Sleep Apnoea ◽  
The Body ◽  
Short Term ◽  
Major Health ◽  
Targeted Drug ◽  
Health Complications ◽  
New Generation ◽  
Oral Supplements

Obesity is a medical condition arises as a result of an imbalance between lipolysis and lipogenesis which leads to accumulation of excess fat. Obesity is linked with major health complications such as diabetes, cardiac disorder, cancer, hypertension, sleep apnoea, etc. Weight loss through medication and healthy food balance can prevent obesity and associated disorders. Though, diet based therapy and drugs have short term effect with lacunae. At present, no reliable and established oral supplements are available to take care of obesity. Nanotechnology is a briskly emerging area of science and technology for food modulation at molecular and atomic level. The unique size and superior properties of nanomaterial have huge application in biology and medicine for food and drug development. Nanotechnology is playing an important role in the food industry for unindustrialized improved food, uptake, absorption, and bioavailability of nutrients to the body. Balanced or better-modified nutrients food, restricted calorie measures and commercial availability is geared through Nanoscience for control of obesity. Nanoparticle Targeted drug therapy, particularly for adipose tissue, may provide a new generation formulation for therapeutics of obesity.

scholarly journals Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins

2020 ◽  
Author(s):  
Meenakshisundaram Balasubramaniam ◽  
Robert Shmookler Reis
Keyword(s):  
Small Molecules ◽  
Drug Targeting ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Hiv Treatment ◽  
Investigational Drug ◽  
Docking Simulations ◽  
Investigational Drugs ◽  
Low Toxicity

Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome caused by SARS-CoV-2 (2019-nCoV). While no drugs have yet been approved to treat this disease, small molecules effective against other viral infections are under clinical evaluation for therapeutic abatement of SARS-CoV-2 infections. Ongoing clinical trials include Kaletra (a combination of two protease inhibitors approved for HIV treatment), remdesivir (an investigational drug targeting RNA-dependent RNA polymerase [RdRP] of SARS-CoV-2), and hydroxychloroquine (an approved anti-malarial and immuno-modulatory drug). Since SARS-CoV-2 replication depends on three virally encoded proteins (RdRP, papain-like proteinase, and helicase), we screened 54 FDA-approved antiviral drugs and ~3300 investigational drugs for binding to these proteins using targeted and unbiased docking simulations and computational modeling. Elbasvir, a drug approved for treating hepatitis C, is predicted to bind stably and preferentially to all three proteins. At the therapeutic dosage, elbasvir has low toxicity (liver enzymes transiently elevated in 1% of subjects) and well-characterized drug-drug interactions. We predict that treatment with elbasvir, alone or in combination with other drugs such as grazoprevir, could efficiently block SARS-CoV-2 replication. The concerted action of elbasvir on at least three targets essential for viral replication renders viral mutation to drug resistance extremely unlikely.

scholarly journals Discovery of Drug-like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3

2020 ◽  
Author(s):  
Rajdeep S. Virdi ◽  
Robert V. Bavisotto ◽  
Nicholas C. Hopper ◽  
Nemanja Vuksanovic ◽  
Trevor R. Melkonian ◽  
...  
Keyword(s):  
Small Molecules ◽  
Antiviral Drug ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Molecular Probes ◽  
Structural Protein ◽  
Beta Lactams ◽  
Autodock Vina ◽  
Differential Scanning Fluorimetry ◽  
High Throughput Assay

ABSTRACTSmall molecules that bind the SARS-CoV-2 non-structural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to coronavirus’ ability to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, beta-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using Autodock VINA. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.

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