scholarly journals Pathogenesis and Possible Drug Targets for Covid-19

2020 ◽  
pp. 1-8
Author(s):  
N. Ramesh Kumar ◽  
S. Chitra
Keyword(s):  
Drug Targets ◽  
Angiotensin Receptor Blockers ◽  
Large Family ◽  
Spike Protein ◽  
Alveolar Cells ◽  
Global Pandemic ◽  
Underlying Principle ◽  
Wide Range ◽  
Type Ii Alveolar Cells ◽  
Subsequent Activation

Coronavirus (CoVs) is a large family of enveloped, single-stranded, positive-sense RNA viruses that infect a wide range of vertebrates. They are extensively found in bats and also in many other birds and mammals including humans. SARS-CoV-2 is a global pandemic and originated from Wuhan States of China. The SARS-CoV-2 is more genetically similar to zoonotic SARS-CoV and less similar to MERS-CoV.  The viral surface spike protein of SARS-CoV-2 binds to the human angiotensin-converting enzyme-2 (ACE-2) receptor of Type II alveolar cells of the lungs and it appears to be the major portal of entry by this virus.  The subsequent activation of the spike protein by transmembrane protease-2 and in addition to lung, ACE-2 is highly expressed in heart followed by kidney and intestinal epithelium. SARS-CoV-2 infects more men than women due to ACE-2 receptor on the cells increased with age and generally it was higher in men than in women. The incubation period for this virus varies from place to place and asystematic symptoms are also commonly seen in infected patients. There are a number of pharmaceuticals already being tried and are in different phase levels of testing, but a better understanding of the underlying pathobiology is required. In this circumstance, this article will briefly review the underlying principle for ACE-2 receptor as a specific target. Despite ACE-2 serving as the portal for infection, the role of ACE inhibitors or angiotensin receptor blockers requires further investigation.

scholarly journals Lipid nanoparticle technologies for the study of G protein-coupled receptors in lipid environments

2020 ◽  
Vol 12 (6) ◽  
pp. 1287-1302 ◽  
Author(s):  
Steven Lavington ◽  
Anthony Watts
Keyword(s):  
Membrane Proteins ◽  
G Protein ◽  
Drug Targets ◽  
Large Family ◽  
G Protein Coupled Receptors ◽  
Integral Membrane Proteins ◽  
Lipid Nanoparticle ◽  
Wide Range ◽  
Biophysical Studies ◽  
G Protein Coupled

AbstractG protein-coupled receptors (GPCRs) are a large family of integral membrane proteins which conduct a wide range of biological roles and represent significant drug targets. Most biophysical and structural studies of GPCRs have been conducted on detergent-solubilised receptors, and it is clear that detergents can have detrimental effects on GPCR function. Simultaneously, there is increasing appreciation of roles for specific lipids in modulation of GPCR function. Lipid nanoparticles such as nanodiscs and styrene maleic acid lipid particles (SMALPs) offer opportunities to study integral membrane proteins in lipid environments, in a form that is soluble and amenable to structural and biophysical experiments. Here, we review the application of lipid nanoparticle technologies to the study of GPCRs, assessing the relative merits and limitations of each system. We highlight how these technologies can provide superior platforms to detergents for structural and biophysical studies of GPCRs and inform on roles for protein-lipid interactions in GPCR function.

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

2020 ◽  
Author(s):  
Scott P. Morton ◽  
Joshua L. Phillips
Keyword(s):  
Electrostatic Interactions ◽  
Spike Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Wide Range ◽  
Nasal Secretions ◽  
Novel Virus ◽  
Ph Range ◽  
The Impact

ABSTRACTSARS-CoV-2 is a novel virus that is presumed to have emerged from bats to crossover into humans in late 2019. As the global pandemic ensues, scientist are working to evaluate the virus and develop a vaccine to counteract the deadly disease that has impacted lives across the entire globe. We perform computational electrostatic simulations on multiple variants of SARS-CoV-2 spike protein s1 in complex with human angiotensin-converting enzyme 2 (ACE2) variants to examine differences in electrostatic interactions across the various complexes. Calculations are performed across the physiological pH range to also examine the impact of pH on these interactions. Two of six spike protein s1 variations having greater electric forces at pH levels consistent with nasal secretions and significant variations in force across all five variants of ACE2. Five out of six spike protein s1 variations have relatively consistent forces at pH levels of the lung, and one spike protein s1 variant that has low potential across a wide range of pH. These predictions indicate that variants of SARS-CoV-2 spike proteins and human ACE2 in certain combinations could potentially play a role in increased binding efficacy of SARS-CoV-2 in vivo.

Understanding Schizophrenia: Genetic Causes and Treatment

2019 ◽  
Vol 1 (1) ◽  
pp. 6-12
Author(s):  
Fatima Javeria ◽  
Shazma Altaf ◽  
Alishah Zair ◽  
Rana Khalid Iqbal
Keyword(s):  
Copy Number ◽  
Drug Targets ◽  
Disease Risk ◽  
Mental Disease ◽  
Copy Number Variants ◽  
Aminobutyric Acid ◽  
Epigenetic Mechanisms ◽  
Gamma Aminobutyric Acid ◽  
Wide Range ◽  
Severe Mental Disease

Schizophrenia is a severe mental disease. The word schizophrenia literally means split mind. There are three major categories of symptoms which include positive, negative and cognitive symptoms. The disease is characterized by symptoms of hallucination, delusions, disorganized thinking and speech. Schizophrenia is related to many other mental and psychological problems like suicide, depression, hallucinations. Including these, it is also a problem for the patient’s family and the caregiver. There is no clear reason for the disease, but with the advances in molecular genetics; certain epigenetic mechanisms are involved in the pathophysiology of the disease. Epigenetic mechanisms that are mainly involved are the DNA methylation, copy number variants. With the advent of GWAS, a wide range of SNPs is found linked with the etiology of schizophrenia. These SNPs serve as ‘hubs’; because these all are integrating with each other in causing of schizophrenia risk. Until recently, there is no treatment available to cure the disease; but anti-psychotics can reduce the disease risk by minimizing its symptoms. Dopamine, serotonin, gamma-aminobutyric acid, are the neurotransmitters which serve as drug targets in the treatment of schizophrenia. Due to the involvement of genetic and epigenetic mechanisms, drugs available are already targeting certain genes involved in the etiology of the disease.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

scholarly journals Behavioral medicine challenges in the shadow of a global pandemic

2020 ◽  
Author(s):  
Alyssa T Brooks ◽  
Hannah K Allen ◽  
Louise Thornton ◽  
Tracy Trevorrow
Keyword(s):  
Environmental Factors ◽  
Health Behavior ◽  
Health Behaviors ◽  
Natural Experiment ◽  
Direct Effects ◽  
Global Pandemic ◽  
Wide Range ◽  
Future Data ◽  
Short And Long Term

Abstract Health behavior researchers should refocus and retool as it becomes increasingly clear that the challenges of the COVID-19 pandemic surpass the direct effects of COVID-19 and include unique, drastic, and ubiquitous consequences for health behavior. The circumstances of the pandemic have created a natural experiment, allowing researchers focusing on a wide range of health behaviors and populations with the opportunity to use previously collected and future data to study: (a) changes in health behavior prepandemic and postpandemic, (b) health behavior prevalence and needs amidst the pandemic, and (c) the effects of the pandemic on short- and long-term health behavior. Our field is particularly challenged as we attempt to consider biopsychosocial, political, and environmental factors that affect health and health behavior. These realities, while daunting, should call us to action to refocus and retool our research, prevention, and intervention efforts

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Histone Deacetylase Enzymes as Potential Drug Targets in Cancer and Parasitic Diseases

2006 ◽  
Vol 2006 ◽  
pp. 1-10 ◽  
Author(s):  
Mehdi Ouaissi ◽  
Ali Ouaissi
Keyword(s):  
Transcriptional Activation ◽  
Histone Deacetylases ◽  
Drug Targets ◽  
Large Family ◽  
Current Data ◽  
Functional Study ◽  
Parasitic Diseases ◽  
Antitumor Effects ◽  
Protozoan Infections

The elucidation of the mechanisms of transcriptional activation and repression in eukaryotic cells has shed light on the important role of acetylation-deacetylation of histones mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Another group belonging to the large family of sirtuins (silent information regulators (SIRs)) has an (nicotinamide adenine dinucleotide)NAD+-dependent HDAC activity. Several inhibitors of HDACs (HDIs) have been shown to exert antitumor effects. Interestingly, some of the HDIs exerted a broad spectrum of antiprotozoal activity. The purpose of this review is to analyze some of the current data related to the deacetylase enzymes as a possible target for drug development in cancer and parasitic diseases with special reference to protozoan infections. Given the structural differences among members of this family of enzymes, development of specific inhibitors will not only allow selective therapeutic intervention, but may also provide a powerful tool for functional study of these enzymes.

scholarly journals FlashPlate Scintillation Proximity Assays for Characterization and Screening of DNA Polymerase, Primase, and Helicase Activities

2001 ◽  
Vol 6 (1) ◽  
pp. 39-46 ◽  
Author(s):  
David L. Earnshaw ◽  
Andrew J. Pope
Keyword(s):  
Dna Polymerase ◽  
Drug Targets ◽  
Direct Synthesis ◽  
Enzyme Characterization ◽  
Dna Helicase ◽  
Oligonucleotide Primer ◽  
Replication Proteins ◽  
Dna Primase ◽  
Wide Range ◽  
Complementary Oligonucleotide

DNA replication proteins represent a class of extremely well-established anti-infective drug targets for which improvements in assay technology are required in order to support enzyme characterization, HTS, and structure-activity relationship studies. Replication proteins are conventionally assayed using precipitation/filtration or gelbased techniques, and are not yet all suitable for conversion into homogeneous fluorescence-based formats. We have therefore developed radiometric assays for these enzymes based upon FlashPlate technology that can be applied to a wide range of targets using a common set of reagents. This approach has allowed the rapid characterization of DNA polymerase, DNA primase, and DNA helicase activities. The resultant 96-/384-well microplate assays are suitable for primary HTS, hit selectivity determination, and/or elucidating the mechanism of action of inhibitors. In all cases, biotinylated DNA oligonucleotide substrates were tethered to streptavidin-coated scintillant-embedded FlashPlate wells. Various adaptations were employed for each enzyme activity. For DNA polymerase, a short complementary oligonucleotide primer was annealed to the longer tethered oligonucleotide, and polymerization was measured by incorporation of [3H]-dNTPs onto the growing primer 3′ end. For DNA primase, direct synthesis of short oligoribonucleotides complementary to the tethered DNA strand was measured by incorporation of [3H]-rNTPs or by subsequent polymerase extension with [3H]-dNTPs from unlabeled primers. For DNA helicase, unwinding of a [33P]-labeled oligonucleotide complementary to the tethered oligonucleotide was measured. This robust and flexible system has a number of substantial advantages over conventional assay techniques for this difficult class of enzymes.

Model Child Care Health Policies

2013 ◽  
Author(s):  
Keyword(s):  
Child Care ◽  
Early Education ◽  
Health And Safety ◽  
Large Family ◽  
Health Policies ◽  
After School ◽  
Wide Range ◽  
Before And After ◽  
Care Health ◽  
Child Care Facilities

Significantly revised and updated, the new Model Child Care Health Policies, 5th Edition is a must-have tool to foster adoption and implemenation of best practices for health and safety in group care settings for young children. These settings include early care and education as well as before and after school child care programs. These model policies are intended to ease the burden of writing site-specific health and safety policies from scratch. They cover a wide range of aspects of operation of early education and child care programs. Child care programs of any type can use Model Child Care Health Policies by selecting relevant issues for their operation and modifying the wording to make selected policies appropriate to the specific settings. These settings include early education and child care centers, small and large family child care homes, part day-programs for ill children, facilities that serve children with special needs, school-age child care facilities, and drop-in facilities. The model policies can be adapted for public, private, Head Start, and tuition-funded facilities. All of the most commonly covered health and safety topics the National Association of Child Care Resource and Referral Agencies found in state regulations are included in this guide.

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