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Structural genomics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19860715 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - October 29, 2009 Category: Infectious Diseases Authors: Chen YW Tags: Infect Disord Drug Targets Source Type: journals

Structural genomics and drug discovery for infectious diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Insti...
Source: Infectious Disorders Drug Targets - October 29, 2009 Category: Infectious Diseases Authors: Anderson WF Tags: Infect Disord Drug Targets Source Type: journals

Advances in Mycobacterium tuberculosis Structural Genomics: Investigating Potential Chinks in the Armor of a Deadly Pathogen.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The waning effectiveness of established tuberculosis treatments due to the rise of multi and extensively drug-resistant strains of Mycobacterium tuberculosis, coupled with the synergism of HIV infection, demands basic research efforts to inform focused drug development programs. Structural genomics projects provide rich sources of information for the rational design of anti-tubercular drugs, aiming to exploit unique and novel protein features and interactions based on atomic resolution structures. This review compiles structures of M. tuberculosis proteins elucidated since January 2007 that are promising avenues for dr...
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Chim N, McMath LM, Beeby M, Goulding CW Tags: Infect Disord Drug Targets Source Type: journals

Benefits of Structural Genomics for Drug Discovery Research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe the methodologies, experience and technologies developed by SG, which range from improvements to cloning protocols to improved procedures for crystallographic structure solution that may be applied in "traditional" structural biology laboratories particularly those performing drug discovery. We also discuss the conditions that must be met to convert the present high-throughput structure determination pipeline into a high-output structure-based drug discovery system. PMID: 19594422 [PubMed - as supplied by publisher] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Grabowski M, Chruszcz M, Zimmerman MD, Kirillova O, Minor W Tags: Infect Disord Drug Targets Source Type: journals

Computational Resources for Protein Modelling and Drug Discovery Applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The design of new medications is an intensive, time-consuming and costly process. Over the years, a rational approach that exploits the structural knowledge of a biological target has led to many successes. This procedure can be expedited using computer-aided modelling techniques. The structure-based approach to drug design relies on knowing the three-dimensional structure of the target macromolecule. If an experimental structure has not been determined yet, a good approximation of the protein target structure can be obtained through computational modelling, provided that some structures of its homologues are available...
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Dhaliwal B, Chen YW Tags: Infect Disord Drug Targets Source Type: journals

Human Cytomegalovirus US28: A Functionally Selective Chemokine Binding Receptor.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chemokines are small cytokines that are part of a large family of molecules that bind to G-protein coupled receptors, which, as a family, are the most widely targeted group of molecules in the treatment of disease. Chemokines are critical for recruiting and activating the cells of the immune system during inflammation especially during viral infections. However, a number of viruses including the large herpes virus human cytomegalovirus (HCMV) encode mechanisms to impede the effects of chemokines or has gained the ability to use these molecules to its own advantage. The Human Cytomegalovirus (HCMV)-encoded chemokine rec...
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Vomaske J, Streblow DN Tags: Infect Disord Drug Targets Source Type: journals

Structural Biology of Bacterial Secretion Systems in Gram-negative Pathogens- Potential for New Drug Targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gram-negative bacteria have evolved diverse secretion systems/machineries to translocate substrates across the cell envelope. These various machineries fulfil a wide variety of functions but are also essential for pathogenic bacteria to infect human or plant cells. Secretion systems, of which there are seven, utilize one of two secretion mechanisms: (i) the one-step mechanism, whereby substrates are translocated directly from the bacterial-cytoplasm to the extracellular medium or into the eukaryotic-target cell; (ii) the two-step mechanism, whereby substrates are first translocated across the bacterial-inner membrane; ...
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Durand E, Verger D, Rêgo AT, Chandran V, Meng G, Fronzes R, Waksman G Tags: Infect Disord Drug Targets Source Type: journals

The Seattle Structural Genomics Center for Infectious Disease (SSGCID).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium established to apply structural genomics approaches to potential drug targets from NIAID priority organisms for biodefense and emerging and re-emerging diseases. The mission of the SSGCID is to determine approximately 400 protein structures over the next five years. In order to maximize biomedical impact, ligand-based drug-lead discovery campaigns will be pursued for a small number of high-impact targets. Here we review the center's target selection processes, which include pro-active engagement of the infectious disease...
Source: Infectious Disorders Drug Targets - July 16, 2009 Category: Infectious Diseases Authors: Myler PJ, Stacy R, Stewart L, Staker B, Van Voorhis WC, Varani G, Buchko GW Tags: Infect Disord Drug Targets Source Type: journals

New opportunities to fight against infectious diseases and to identify pertinent drug targets with novel methodologies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19519478 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: de Brevern AG Tags: Infect Disord Drug Targets Source Type: journals

Conservation and divergence among Salmonella enterica subspecies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome sequencing efforts of taxonomically proximate organisms successfully divulged proteomic diversity embedded within closely related organisms. The Salmonella enterica subspecies represents a group of enterobacteric pathogens known to share similar genomic content yet possess diverse host specificity and distinct disease symptoms. Study of Salmonella enterica subspecies proteomes reports an overestimation of the proximity among the subspecies. Interestingly, orthology comparison among Salmonella typhi and Salmonella typhimurium across the proteome suggested the metabolic proteins possessed the highest propensity of...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Bhaduri A, Kalaimathy S, Sowdhamini R Tags: Infect Disord Drug Targets Source Type: journals

Evolutionary divergence of Plasmodium falciparum: sequences, protein-protein interactions, pathways and processes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this article we review the organism-wide biological data available for Plasmodium falciparum (P. falciparum), a malarial parasite, in relation to the data available for other organisms. We provide comparisons at different levels such as amino acid sequences of proteins encoded in the genomes, protein-protein interaction features, metabolic and signaling pathways and processes. Our comparative analyses highlights that P. falciparum is highly diverged compared to most other eukaryotes at all these levels. Despite the extensive variation some of the physical associations between proteins, such as RNA polymerase complex...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Tyagi N, Swapna LS, Mohanty S, Agarwal G, Gowri VS, Anamika K, Priya ML, Krishnadev O, Srinivasan N Tags: Infect Disord Drug Targets Source Type: journals

The euHCVdb suite of in silico tools for investigating the structural impact of mutations in hepatitis C virus proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hepatitis C is a viral infection of the liver that results in acute hepatitis and chronic liver disease, including cirrhosis and liver cancer. An estimated 170 million persons are chronically infected worldwide. The Hepatitis C virus is the pathogen agent responsible for hepatitis C. HCV is an enveloped RNA-positive virus of the flaviviridae family. The HCV genome shows remarkable sequence variability. This variability leads to the classification of HCV into 6 genotypes, numerous subtypes and HCV exists in each infected patient as quasi-species. The genotype may be linked to the severity of the disease and to the effic...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Combet C, Bettler E, Terreux R, Garnier N, Deléage G Tags: Infect Disord Drug Targets Source Type: journals

HIV co-receptor CCR5: structure and interactions with inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The CC-chemokine receptor 5 (CCR5), a membrane protein belonging to the G-protein coupled receptor super-family, has been identified as an essential co-receptor for HIV entry into the cells, and small molecules that inhibit HIV entry by targeting CCR5 have been in fast development as antiviral agents. This review focuses on computational studies of predicting the CCR5 structure and its interactions with known small molecule inhibitors and discusses how the recently solved GPCR structures would provide new insights into the modeling of CCR5-inhibitor binding. In addition, this review pays a particular attention to the d...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Wang T, Duan Y Tags: Infect Disord Drug Targets Source Type: journals

In silico studies on DARC.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Duffy Antigen/Receptor for Chemokine (DARC) is a seven segment transmembrane protein. It was firstly discovered as a blood group antigen and was the first specific gene locus assigned to a specific autosome in man. It became more famous as an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi), and finally for chemokines. DARC is an unorthodox chemokine receptor as (i) it binds chemokines of both CC and CXC classes and (ii) it lacks the Asp-Arg-Tyr consensus motif in its second cytoplasmic loop hence cannot couple to G proteins and activate their signaling pathways. DARC had also b...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: de Brevern AG, Autin L, Colin Y, Bertrand O, Etchebest C Tags: Infect Disord Drug Targets Source Type: journals

Antimalarial drug discovery: in silico structural biology and rational drug design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Malaria remains one of the most burdensome human infectious diseases, with a high rate of resistance outbreaks and a constant need for the discovery of novel antimalarials and drug targets. For several reasons, Plasmodial proteins are difficult to characterise structurally using traditional physical approaches. However, these problems can be partially overcome using a number of in silico approaches. This review describes the peculiarities of malaria proteins and then details various in silico strategies to select and allow descriptions of the molecular structures of drug target candidates as well as subsequent rational...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: de Beer TA, Wells GA, Burger PB, Joubert F, Marechal E, Birkholtz L, Louw AI Tags: Infect Disord Drug Targets Source Type: journals

Computational biology in anti-tuberculosis drug discovery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The resurgence of drug resistant tuberculosis (TB) is a major global healthcare problem. Mycobacterium tuberculosis (MTB), TB's causative agent, evades the host immune system and drug regimes by entering prolonged periods of nonproliferation or dormancy. The identification of genes essential to the bacterium in its dormancy phase infections is a key strategy in the development of new anti-TB therapeutics. The rapid expansion of TB-related genomic data sources including DNA sequences, transcriptomic and proteomic profiles, and genome-wide essentiality data, present considerable opportunities to apply advanced computatio...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Murphy DJ, Brown JR Tags: Infect Disord Drug Targets Source Type: journals

New approaches to structure-based discovery of dengue protease inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dengue virus (DENV), a member of the family Flaviviridae, presents a tremendous threat to global health since an estimated 2.5 billion people worldwide are at risk for epidemic transmission. DENV infections are primarily restricted to sub-tropical and tropical regions; however, there is concern that the virus will spread into new regions including the United States. There are no approved antiviral drugs or vaccines to combat dengue infection, although DENV vaccines have entered Phase 3 clinical trials. Drug discovery and development efforts against DENV and other viral pathogens must overcome specificity, efficacy, saf...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Tomlinson SM, Malmstrom RD, Watowich SJ Tags: Infect Disord Drug Targets Source Type: journals

A review of MED-SuMo applications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Resolved three-dimensional protein structures are a major source of information for understanding protein functional properties. The current explosive growth of publicly available protein structures is producing large volumes of data for computational modelling and drug design methods. Target-based in silico drug design tools aid design and optimize compounds to bind to specific targets. MED-SuMo is a powerful technology for comparing local regions on protein surfaces, allowing similarities to be discovered and explored. This is a target-based tool that can exploit all available macromolecule structures. Its computatio...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Doppelt-Azeroual O, Moriaud F, Adcock SA, Delfaud F Tags: Infect Disord Drug Targets Source Type: journals

Innovative in silico approaches to address avian flu using grid technology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recent years have seen the emergence of diseases which have spread very quickly all around the world either through human travels like SARS or animal migration like avian flu. Among the biggest challenges raised by infectious emerging diseases, one is related to the constant mutation of the viruses which turns them into continuously moving targets for drug and vaccine discovery. Another challenge is related to the early detection and surveillance of the diseases as new cases can appear just anywhere due to the globalization of exchanges and the circulation of people and animals around the earth, as recently demonst...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Breton V, da Costa AL, de Vlieger P, Kim YM, Maigne L, Reuillon R, Sarramia D, Truong NH, Nguyen HQ, Kim D, Wu YT Tags: Infect Disord Drug Targets Source Type: journals

Interactive text mining with Pipeline Pilot: a bibliographic web-based tool for PubMed.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Text mining has become an integral part of all research in the medical field. Many text analysis software platforms support particular use cases and only those. We show an example of a bibliographic tool that can be used to support virtually any use case in an agile manner. Here we focus on a Pipeline Pilot web-based application that interactively analyzes and reports on PubMed search results. This will be of interest to any scientist to help identify the most relevant papers in a topical area more quickly and to evaluate the results of query refinement. Links with Entrez databases help both the biologist and the chemi...
Source: Infectious Disorders Drug Targets - May 31, 2009 Category: Infectious Diseases Authors: Vellay SG, Latimer NE, Paillard G Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in viral infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19275697 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Sabatier JM Tags: Infect Disord Drug Targets Source Type: journals

Antiviral treatment of chikungunya virus infection.Email this article to a colleague. Save this article to My Clippings. discuss this article 1 CommentDiscuss or comment on this article.
Chikungunya virus is a typical emerging virus which has been responsible for several million cases of human infections since 2004. No antiviral treatment is currently available. The antimalarial chloroquine has been used in the past but recent studies suggest that it is not or poorly active in vivo. A number of tracks are currently under investigation (inhibition of viral enzymes, of virus entry or maturation, enhancement of immunological response) and new animal models have been made available, including a mouse model and a non-human primate model. We review here the main perspectives of chikungunya antiviral treatmen...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: de Lamballerie X, Ninove L, Charrel RN Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in hepatitis B virus infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hepatitis B virus infection (HBV) is a significant global health problem. Despite the success of universal hepatitis B vaccination in many countries, more than 350 million individuals worldwide are chronically infected and 15- 40% of those will develop cirrhosis and/or hepatocellular carcinoma if left untreated. Available therapies for chronic hepatitis B (CHB) infection are effective at decreasing viremia and improving measured clinical outcomes, however, no single therapy is optimal. As such, alternative drug therapies and the investigation of their role in the management of CHB are warranted. Significant improvement...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Stein LL, Loomba R Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in herpes simplex and epstein barr virus infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Herpes simplex virus (HSV) and Epstein Barr Virus (EBV) are Herpesviridae. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. EBV infections are also often asymptomatic but this virus may be associated to carcinoma in immunocompetent patients and to severe diseases in immunocompromised patients. These viruses establish latency, in neuronal cells for HSV and in B-cells for EBV, and may reactivate, with or without symptoms. There are few drugs licensed for the treatment of HSV infections. Most of them target the viral DNA polymerase, in which acyclo...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Billaud G, Thouvenot D, Morfin F Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in rhinoviral infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human Rhinoviruses (HRV) are by far the most common respiratory viruses responsible for most cases of the common cold and important pathogens in acute exacerbations of asthma and COPD. The molecular pathogenesis of HRV infection is quite completely understood. However there is still no approved specific treatment against HRV infections. The aim of this article is therefore to give an overview of the principles of rhinovirus infection, the associated therapeutic targets and to review up-to-date virus-specific clinical trials. PMID: 19275701 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Rohde G Tags: Infect Disord Drug Targets Source Type: journals

New drug targets for hepatitis C and other flaviviridae viruses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Flaviviridae family comprises the genus Flavivirus, Hepacivirus and Pestivirus. These viruses are responsible for considerable human and animal disease and mortality worldwide. Flaviviruses cause a range of acute febrile illnesses along with encephalitic or haemorrhagic diseases. Chronic hepatitis C virus (HCV) infection is the most important hepacivirus human disease and remains a global health threat with nearly 200 million carriers worldwide. Current treatment consists in the use of peginterferon alfa (pegIFN) plus ribavirin (RBV) for 24 to 72 weeks, depending on HCV genotype, baseline viral load and the achieve...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Paula T, Pablo R, Eugenia V, Pablo B, Sabino P, José M, Antonio M, Dolores HM, Pablo L, Javier GS, Vincente S Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in infections with other emerging viruses: influenza viruses, metapneumovirus and hantaviruses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Among emergent and re-emergent viral infections, influenza, hemorrhagic fevers, including hantaviruses, constitute one of the major threats to human beings. Advances in immunopathogenesis of these viral infections have improved initial supportive treatments and led to recognition and adoption of several useful antiviral agents. This review focuses on therapeutic and preventive aspects of these viral infections, and evaluates old and new promising agents are in the pipeline of pharmaceutical companies, and finally addresses therapeutic aspects in the treatment of these viral pathogens. However, it should be stressed tha...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Torre D, Pugliese A Tags: Infect Disord Drug Targets Source Type: journals

Drug Targets in Human T-Lymphotropic Virus Type 1 (HTLV-1) Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human T-lymphotropic virus type 1 (HTLV-1), the first known human retrovirus, induces various human diseases with a long latency period. The mechanism by which the virus causes diseases is still unknown. Studies indicate that viral replication is important at least for the development of HTLV-1 associated myelopathy, and therefore treatments based on our knowledge of human immunodeficiency virus type-1 (HIV-1) can be utilized to develop potent antiretroviral therapies targeting the replication enzymes reverse transcriptase, protease and integrase as well as the envelope glycoproteins. Furthermore, accessory gene produc...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Boross P, Bagossi P, Weber IT, Tözsér J Tags: Infect Disord Drug Targets Source Type: journals

Sequencing of Therapy to Avoid Resistance and the Need for New Antiretroviral Drugs in the Treatment of HIV Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HIV-1 drug regimens now offer more potent, less toxic and more durable choices. However, strategies addressing convenient sequential use of active antiretroviral combinations are rarely presented in the literature. Studies have seldom directly addressed this issue, despite it being a matter of daily use in clinical practice. This is, in part, because of the complexity of HIV-1 resistance information. Nevertheless, several principles can effectively assist the planning of antiretroviral drug sequencing. The introduction of tenofovir, abacavir and emtricitabine into current nucleoside backbone options, with each of them ...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Wainberg MA, Martinez-Cajas JL Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in infections with ebola and marburg viruses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of antiviral drugs for Ebola and Marburg viruses has been slow. To date, beyond supportive care, no effective treatments, prophylactic measures, therapies, or vaccines are approved to treat or prevent filovirus infections. In this review, we examine the current treatments available to administer care for filovirus infection, the potential therapeutic targets that can be used for filovirus drug development, and the various drug targeting techniques used against filoviruses. PMID: 19275706 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Gene OG, Julia BE, Vanessa MR, Victoria WJ, Thomas GW, Lisa HE Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in cytomegalovirus infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human cytomegalovirus (HCMV) infections are usually benign and self-limiting in the immunocompetent population; however, HCMV is a well-recognized problem among immunocompromised patients (in particular immunosuppressed patients with stem cell or solid organ transplantation, AIDS, or cancer). In this group of patients, HCMV infections are a significant cause of morbidity and mortality. Additionally, congenital HCMV infections are a leading cause of birth defects and infections in children, occurring in 1 to 2% of all live births. Currently available drugs for the treatment of HCMV diseases in the immunocompromised host...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Andrei G, De Clercq E, Snoeck R Tags: Infect Disord Drug Targets Source Type: journals

Drug Targets in Severe Acute Respiratory Syndrome (SARS) Virus and other Coronavirus Infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Coronaviruses are important human and animal pathogens of the order Nidovirales. Several new members were discovered following the emergence of SARS-CoV in human populations, including two human coronaviruses and several animal coronaviruses. They cause respiratory and gastrointestinal illnesses and have been found in the brains of patients with multiple sclerosis. The high mortality of SARS, the identification of a natural reservoir, and the well-founded fear of provoking antibody-enhanced disease as a result of vaccination fueled the ongoing efforts in anti-coronavirus drug discovery. This review presents the results...
Source: Infectious Disorders Drug Targets - March 1, 2009 Category: Infectious Diseases Authors: Tong TR Tags: Infect Disord Drug Targets Source Type: journals

Inhibition of prion amplification by expression of dominant inhibitory mutants--a systematic insertion mutagenesis study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The ...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Geissen M, Mella H, Saalmüller A, Eiden M, Proft J, Pfaff E, Schätzl HM, Groschup MH Tags: Infect Disord Drug Targets Source Type: journals

Drug targets in prion diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19200009 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Schätzl HM Tags: Infect Disord Drug Targets Source Type: journals

Therapy in prion diseases: from molecular and cellular biology to therapeutic targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prion diseases are infectious and fatal neurodegenerative disorders of man and animals which are characterized by spongiform degeneration in the central nervous system. In human diseases, the manifestation can be sporadic, familial or acquired by infection. Prion disorders are caused by the accumulation of an aberrantly folded isoform of the cellular prion protein (PrP(c)), commonly named PrP(Sc). Although prion diseases are usually rare, they have the potential to be transferred within and also between species by infection processes, giving then raise even to epidemic scenarios. As pathology is obviously restricted to...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Krammer C, Vorberg I, Schätzl HM, Gilch S Tags: Infect Disord Drug Targets Source Type: journals

Amyloidophilic compounds for prion diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent outbreaks of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease have aroused great concern in many countries and have necessitated the development of suitable therapies. We have demonstrated that sulfated glycans such as pentosan polysulfate and fucoidan, and amyloidophilic compounds such as amyloid dye derivatives, styrylbenzoazole derivatives, and phenylhydrazine derivatives have efficacies in prion-infected animals. Amyloidophilic compounds present potentialities not only as therapeutic candidates but also as prion amyloid imaging probes for use in nuclear medicine technology such as p...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Teruya K, Kawagoe K, Kimura T, Chen CJ, Sakasegawa Y, Dohura K Tags: Infect Disord Drug Targets Source Type: journals

Tetracyclines and prion infectivity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article analyzes the development of tetracyclines as a therapeutic tool in TSE in the light of recent results obtained in our laboratories. PMID: 19200012 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Forloni G, Salmona M, Marcon G, Tagliavini F Tags: Infect Disord Drug Targets Source Type: journals

Procedure for identification and characterization of drugs efficient against Mammalian prion: from a yeast-based antiprion drug screening assay to in vivo mouse models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prion diseases are fatal and incurable infectious neurodegenerative disorders affecting humans and other mammals. Prions are composed essentially if not solely of PrP(Sc), a misfolded form of the host-encoded PrP protein. PrP(Sc) catalyzes the transconformation of the normal endogenous PrP (PrP(C)) into more PrP(Sc). Prion replication thus corresponds to the propagation of an altered folding state of PrP. Several prion proteins have also been identified in the simple model organism Saccharomyces cerevisiae. Yeast prion-based screening assays have allowed identification of drugs active against mammalian prions, thus rev...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Voisset C, Saupe SJ, Galons H, Blondel M Tags: Infect Disord Drug Targets Source Type: journals

Inhibition of prion amplification by expression of dominant inhibitory mutants - a systematic insertion mutagenesis study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Until now it is still not clear which structural elements of the prion protein (PrP) are involved in its conversion process. Characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit PrP(res) formation by dominant inhibitory mutations. To address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3F4-tagged PrP. The mutants were expressed by retroviral transduction in three different scrapie infected cell lines (ScN2a; SMB[RC040]; SMB[22F]). The ...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Geissen M, Mella H, Saalmüller A, Eiden M, Proft J, Pfaff E, Schätzl HM, Groschup MH Tags: Infect Disord Drug Targets Source Type: journals

Preventing prion pathogenicity by targeting the cellular prion protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prions are unique in that the infectious particles contain no detectable nucleic acid and appear to consist of aggregated forms of misfolded cellular prion protein. Prions form distinct strains and can transmit disease between species. Whilst the molecular basis of prion diseases is beginning to be unravelled, much remains unknown including the atomic structure of the infectious and toxic species. In contrast, the structure and folding properties of the cellular prion protein are well characterised and, although its precise function remains enigmatic, constitutive knockout of protein expression in mice produces apparen...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Nicoll AJ, Collinge J Tags: Infect Disord Drug Targets Source Type: journals

Gene and cell therapy for prion diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal prion protein named PrP(Sc). PrP(Sc) results from the post-translational conformational modification of the host-encoded protein PrP(C). To date there is no treatment for this inexorably fatal disease. Hence, a major focus of research consists in the identification of new molecules that could interfere with in vivo prion propagation. Promising therapeutic approaches to block the production of PrP(Sc) are based on PrP RNA interference, passive or active immunization, dominant negative inhibition of PrP(Sc) formation, as well ...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Relaño-Ginés A, Gabelle A, Lehmann S, Milhavet O, Crozet C Tags: Infect Disord Drug Targets Source Type: journals

LRP/LR as an Alternative Promising Target in Therapy of Prion Diseases, Alzheimer's Disease and Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The 37 kDa/67 kDa laminin receptor (LRP/LR) represents a key player for cell adhesion, is associated with the metastatic potential of solid tumors and is required for maintenance of cell viability by preventing apoptosis. LRP/LR acts as a receptor for viruses such as Sindbis virus, Venezuelean Equine Encephalitis (VEE) virus, Adeno-associated-viruses (AAV) and Dengue Virus, the latter causing 50 to 100 million infections in humans per year. LRP/LR acts further as a receptor for prions and represents a multifunctional protein subcellularly located to the nucleus, the cytoplasm and the cell surface. The receptor represen...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Vana K, Zuber C, Pflanz H, Kolodziejczak D, Zemora G, Bergmann AK, Weiss S Tags: Infect Disord Drug Targets Source Type: journals

Recent advances in prion chemotherapeutics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. Many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. However, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. There is increasing pressure to find effective decontaminants for blood supplies, as variant Creutzfeldt Jakob Disease (vCJD) has been sh...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Sim VL, Caughey B Tags: Infect Disord Drug Targets Source Type: journals

Therapeutic Trials in Human Transmissible Spongiform Encephalo-pathies: Recent Advances and Problems to Address.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The progress in understanding disease pathology and phenomenology in prion disorders and recent advances in diagnostic techniques might allow researchers to think about therapeutic trials in CJD patients. Some attempts have been made in the past. Drugs tested involved a variety of compounds, which belong to antimicrobial, antiinflammatory or analgesic substance classes. Most papers on this subject describe single case reports. Controlled trials are virtually not available and a double-blinded study was published for flupirtine only. Despite it has been demonstrated that a clinical trial is feasible, the clinicians migh...
Source: Infectious Disorders Drug Targets - February 1, 2009 Category: Infectious Diseases Authors: Zerr I Tags: Infect Disord Drug Targets Source Type: journals

New strategies and tools to identify drug targets on infectious disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19075795 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Garcia-Sanz JA Tags: Infect Disord Drug Targets Source Type: journals

Th17 and treg cells, two new lymphocyte subpopulations with a key role in the immune response against infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In addition to the T helper 1 (Th1) and Th2 lymphocyte subsets, two new subpopulations Th17 and regulatory T (Treg) cells have recently been described. Th17 cells, which produce high levels of interleukin (IL)-17, are dependent on the transcription factor orphan nuclear receptor RORC2/RORgammat and have been implicated in exacerbating the immune response to infections. Conversely, Treg cells, either thymus-derived or generated upon TCR activation of naîve T cells, express the transcription factor forkhead box P3 (Foxp3) and have regulatory functions mediated through either direct cell-cell contact or immuno-suppre...
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Vernal R, Garcia-Sanz JA Tags: Infect Disord Drug Targets Source Type: journals

Toll like receptor - potential drug targets in infectious disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Toll like receptors (TLR) play a critical role in the recognition and response of pathogens by the innate immune system. Pathogen engagement of the TLR-MyD88 pathway favours the development of a protective Th1-biased T cell response. Interruption of TLR recognition or signalling has profound effects on innate immunity. Agonists or antagonists of specific TLRs modulate the host response to microbial infections and have effects beyond infectious control and may be used as immunostimulators in vaccine, cancer, inflammatory disorders and allergy. PMID: 19075797 [PubMed - in process] (Source: Infectious Disorders Drug Targets)
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Erard F, Ryffel B Tags: Infect Disord Drug Targets Source Type: journals

Transient Responses Via Regulation of mRNA Stability as an Immuno-logical Strategy for Countering Infectious Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Posttranscriptional regulation of gene expression plays a pivotal role as a fast control system for T-cells and B-cells operating in the defense reactions against rapidly growing infectious agents. The framework of this machinery involves cis-acting elements in the mRNAs of relevant cytokines and trans-acting factors interacting with these elements. The cis- and trans-acting factors enforce rapid mRNA decay with other proteins such as nucleases in the decay machinery. The most prominent cis-element contains A + U- rich sequence (ARE), and is located in the 3'-untranslated region of the target mRNAs. Some ARE-binding pr...
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Nakagawa J Tags: Infect Disord Drug Targets Source Type: journals

Differential splicing, disease and drug targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genome complexity and diversity can be due to Alternative Splicing (AS), a process by which one gene can generate multiple mRNA isoforms and then several proteins. This is part of a normal process of variation on an individual, and when it is disrupted or modified, may trigger disease. To date, there are many pathologies described due to the effects of altered splicing isoforms, and effort is focused on the description of new ones. The design of drug target has to consider splicing, as in many occasions, a drug might have effect on different isoforms, instead of on the particular one implicated in the pathology. Intere...
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Villate O, Rastrojo A, López-Díez R, Hernández-Torres F, Aguado B Tags: Infect Disord Drug Targets Source Type: journals

Translation Controlled mRNAs: New Drug Targets in Infectious Diseases?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent data from a series of laboratories has pinpointed the relevant role of translation control on the regulation of gene expression. In particular, an analysis of T cell activation has led to demonstrate that during this physiological transition about 20% of the regulated mRNAs are controlled at the translation level. Furthermore, modulating the host mRNA translation is one of the mechanisms used by infectious agents to achieve a productive infection. In the present review, we summarize the current knowledge on the translation machinery, the translational control mechanisms during the immune response, as well as the...
Source: Infectious Disorders Drug Targets - December 1, 2008 Category: Infectious Diseases Authors: Diaz-Guerra E, Vernal R, Cantero W, Müllner EW, Garcia-Sanz JA Tags: Infect Disord Drug Targets Source Type: journals