Abstract:
:These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this biological information rich and functional knowledge poor scenario, the challenges are indeed grand, no less than the assembly of the genome of the whole organism. These include functional annotation of genes, identification of druggable targets, prediction of three-dimensional structures of protein targets from their amino acid sequences, arriving at lead compounds for these targets followed by a transition from bench to bedside. We propose here a "Genome to Hits In Silico" strategy (called Dhanvantari) and illustrate it on Chikungunya virus (CHIKV). "Genome to hits" is a novel pathway incorporating a series of steps such as gene prediction, protein tertiary structure determination, active site identification, hit molecule generation, docking and scoring of hits to arrive at lead compounds. The current state of the art for each of the steps in the pathway is high-lighted and the feasibility of creating an automated genome to hits assembly line is discussed.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Soni A,Pandey KM,Ray P,Jayaram Bdoi
10.2174/13816128113199990379subject
Has Abstractpub_date
2013-01-01 00:00:00pages
4687-700issue
26eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20121218-2journal_volume
19pub_type
杂志文章,评审abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availabilit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612053382377
更新日期:2005-01-01 00:00:00
abstract::The skin is often introduced as the largest organ of the human body which - being uniquely exposed to external stress - faces several types of challenges, from physical, chemical, biological, and immunological origin. Therefore, the skin is also a site where inflammation, oxidative stress and cellular damage occurs re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180717155953
更新日期:2018-01-01 00:00:00
abstract::Telomerase is a specialized enzymatic complex responsible for the synthesis of telomeric repeats 5'-TTAGGG-3' localized at the ends of eukaryotic chromosomes. This mechanism prevents shortening of telomeres after each cell division. The enzyme is detected in about 85% of human tumors, but it is not expressed in normal...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140630092721
更新日期:2014-01-01 00:00:00
abstract::Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to abnormalities in transepithelial ion transport in the airways of affected patients. Lung disease is the major contributor to morbidity and mortality in patients with cystic fibrosis but recommende...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799315984
更新日期:2012-01-01 00:00:00
abstract::Glioblastoma (GBM) is a deadly tumor, which in spite of surgery and radio/chemotherapy frequently undergoes relapses related to the infiltration of the normal parenchyma and to resistance to cytotoxic and radiation therapy. Immunotherapy may represent a promising approach, which may complement existing therapies with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797249206
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, chocolate and beverages such as coffee, tea and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnes...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180130112652
更新日期:2018-01-01 00:00:00
abstract::RNA interference (RNAi) has quickly proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms that possess the required set of proteins of the interference pathway. In protozoan parasites like Plasmodium, Toxoplasma, Entamoeba, Giardia, Trypanosom...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990027
更新日期:2014-01-01 00:00:00
abstract::The most important glycoproteins of trypanosomatids are anchored by glycoinositolphospholipids (GIPLs) to their plasma membrane. In addition, free GIPLs have been described, for instance the lipopeptidophosphoglycan (LPPG) which is a major component of the surface of T. cruzi epimastigotes. An inositolphosphoceramide ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397519
更新日期:2001-08-01 00:00:00
abstract::Neuregulin1 proteins (NRG1s) are epidermal growth factor (EGF) family members which are ligands for the ErbB receptor tyrosine kinases (RTKs). A decade of research has revealed that the NRG1-ErbB signaling is essential for the cardiac development and pivotal for maintaining the physiological function of the adult hear...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796391010
更新日期:2011-01-01 00:00:00
abstract::The so-called hygiene hypothesis is, at least in part, accountable for the increase in allergic diseases in the developed countries. Although there is support for one of its primary predictions that host-microbe interactions in early life have longterm effects on the development of disease across populations, the theo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800166031
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased inc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181009105305
更新日期:2018-01-01 00:00:00
abstract::Human tryptase is a structurally unique and mast cell specific trypsin-like serine protease. Recent biological and immunological investigations have implicated tryptase as a mediator in the pathology of numerous allergic and inflammatory conditions including rhinitis, conjunctivitis, and most notably asthma. A growing...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 00:00:00
abstract::Although somewhat controversial, there is good evidence that long-distance travel in general is a risk factor for venous thromboembolism, even in the absence of other risk factors. This is probably due to effects consequent to prolonged sitting but air travel in particular may be associated with risk factors other tha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781662966
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Stroke represent one of the most devastating of all neurological diseases, affecting about 15 million people per year and is an important cause of morbidity and mortality worldwide and currently the leading cause of adult disability in developed countries. Blood pressure and heart rate may undergo several mo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170714162455
更新日期:2017-01-01 00:00:00
abstract::The typical way of judging about either the efficacy of a new treatment or, on the contrary, the damage of a pollutant agent is through a test of hypothesis having its ineffectiveness as null hypothesis. This is the typical operational field of Kolmogorov's statistical framework where wastes of data (for instance non ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780765891
更新日期:2007-01-01 00:00:00
abstract::Over the last years a number of reports have described elevated numbers of regulatory T (Treg) cells inside of tumors, in close proximity of the tumor, draining lymph nodes and also in peripheral blood of patients with solid tumors and hematologic malignancies. There is increasing evidence that Treg cells can migrate ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788453211
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:In spite of considerable efforts of researchers the cancer deseases remain to be incurable and a percentage of cancer deseases in the structure of mortality increases every year. At that, high systemic toxicity of antitumor drugs hampers their effective use. Because of this fact, the development of nanosyste...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190117095132
更新日期:2018-01-01 00:00:00
abstract::The heart is a sophisticated endocrine gland synthesizing a family of peptide hormones by three different genes. These cardiac hormones are stored as 3 prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP prohormones are 4 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790963887
更新日期:2010-01-01 00:00:00
abstract::Histone deacetylases (HDACs), which act on acetylated histones and/or other non-histone protein substrates, represent validated epigenetic targets for the treatment of cancer and other human diseases. The inhibition of HDAC activity was shown to induce cell cycle arrest, differentiation, apoptosis as well as a decreas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141110164604
更新日期:2015-01-01 00:00:00
abstract::Chemokines and their receptors play critical roles in leukocyte trafficking during inflammatory processes. Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582165
更新日期:2009-01-01 00:00:00
abstract::Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789909665
更新日期:2009-01-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788168146
更新日期:2009-01-01 00:00:00
abstract::The clinically most relevant medications for lipid management are the statins, which constitute in the majority of the cases the basis of any lipid-modulating therapy. However, other agents are often needed to either reduce low-density cholesterol to target levels and/or to treat residual serum lipoprotein abnormaliti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319170017
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND & AIMS:Nowadays, the world is facing a common problem that the population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people, has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal li...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200605111232
更新日期:2020-01-01 00:00:00
abstract::Currently management of food allergy is mainly based on absolute avoidance of the offending food(s) and the use of rescue medication. However, the risk of severe or life-threatening reactions due to inadvertent exposure, nutritional imbalance and social isolation raises the demand of disease-modifying treatments. The ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990045
更新日期:2014-01-01 00:00:00
abstract::Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788923804
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612825666190702095612
更新日期:2019-01-01 00:00:00
abstract::Hyperuricemia, has been traditionally related to nephrolithiasis and gout. However, it has also been associated with the development of type 2 diabetes mellitus (T2DM) and cardiometabolic and cardiovascular diseases. Pathophysiologically, elevated serum uric acid (SUA) levels may be associated with abnormal lipid and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612827666210104124320
更新日期:2021-01-04 00:00:00
abstract::We herein reviewed the mechanism underlying the gastric hyperemic response following barrier disruption, with a focus on cyclooxygenase (COX) isozymes, prostaglandin (PG) E2, and capsaicin-sensitive afferent neurons. Mucosal damage was induced by exposing the stomach to 20 mM taurocholate (TC) with 50 mM HCl. The TC t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150514105248
更新日期:2015-01-01 00:00:00