Current drug targets. Infectious disorders最新文献_第3页

CD8+ T-cells: are they sufficient to prevent, contain or eradicate HIV-1 infection? CD8+ t细胞是否足以预防、控制或根除HIV-1感染?

Current drug targets. Infectious disorders Pub Date : 2005-06-01 DOI: 10.2174/1568005054201571

Scott A Brown, Julia L Hurwitz, Xiaoyan Zhan, Peter C Doherty, Karen S Slobod

引用次数: 9

The HIV pandemic: a forgotten crisis? 艾滋病毒大流行:被遗忘的危机?

Current drug targets. Infectious disorders Pub Date : 2005-06-01 DOI: 10.2174/1568005054201607

Maxwell Madzikanga, Abigail Kangwende, John Pfumojena, Karen S Slobod, Julia L Hurwitz

引用次数: 1

HIV vaccine discovery and development. 艾滋病毒疫苗的发现和开发。

Current drug targets. Infectious disorders Pub Date : 2005-06-01 DOI: 10.2174/1568005054201526

Julia L Hurwitz

引用次数: 1

HIV-1 envelope evolution and vaccine efficacy. HIV-1包膜进化和疫苗效力。

Current drug targets. Infectious disorders Pub Date : 2005-06-01 DOI: 10.2174/1568005054201553

D E Mosier

{"title":"HIV-1 envelope evolution and vaccine efficacy.","authors":"D E Mosier","doi":"10.2174/1568005054201553","DOIUrl":"https://doi.org/10.2174/1568005054201553","url":null,"abstract":"Transmission of human immunodeficiency virus type 1 (HIV-1) selects for envelope variants with a number of defined properties, including use of CCR5 as the preferred coreceptor, binding to CCR5 in a distinct manner compared to HIV-1 isolated later in infection, shorter variable (V) regions, and fewer N-linked glycosylation sites. These features define the ideal target for an envelope-containing vaccine designed to elicit neutralizing antibody. If a candidate vaccine were sufficiently potent to elicit sterilizing immunity, virus evolution would not be an issue. However, all results to date suggest that an envelope-containing vaccine will have a lesser impact, and that virus evolution will contribute to escape from the vaccine-induced antibody response. The key question is whether or not the early selection pressure imposed by neutralizing antibody will have a long term impact on HIV disease progression. Several recent reports suggest that HIV-1 will evolve to rapidly escape antibody selection, and that the cost to the virus in terms of entry fitness will be small. Durable effects of vaccination are predicted to be associated with a reduction in peak viremia and viral set point at the time of primary infection.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 2","pages":"171-7"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005054201553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25153129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

PDF inhibitors: an emerging class of antibacterial drugs. PDF抑制剂:一类新兴的抗菌药物。

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174618

K W Johnson, D Lofland, H E Moser

{"title":"PDF inhibitors: an emerging class of antibacterial drugs.","authors":"K W Johnson, D Lofland, H E Moser","doi":"10.2174/1568005053174618","DOIUrl":"https://doi.org/10.2174/1568005053174618","url":null,"abstract":"The metalloenzyme peptide deformylase (PDF) represents one of the most promising bacterial targets in the search for novel mode of action antibiotics that lack cross-resistance to existing drugs. Initial research and clinical development has focused on anti-pneumococcal applications. During optimization, peptide analogs were developed containing either a hydroxamate or formyl-hydroxylamine as metal interacting group, yielding inhibitors with in vitro activity against a broad spectrum of organisms. Preclinical studies revealed potent antibacterial activity in vivo that is paired with good pharmacokinetic properties and excellent tolerability in different species. BB-83698, a potent PDF inhibitor with i.v. and oral efficacy in preclinical animal models, represents the first class-representative compound evaluated in man. The inhibitor was administered by i.v. infusion and was shown to exhibit generally dose-proportional pharmacokinetics. It was well tolerated up to doses providing predicted therapeutic exposures. These human results, combined with the preclinical information, clearly support the potential of PDF inhibitors for development as a novel class of antibacterial therapeutics.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 1","pages":"39-52"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005053174618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25014857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 34

Amino acid metabolic routes in Trypanosoma cruzi: possible therapeutic targets against Chagas' disease. 克氏锥虫氨基酸代谢途径:治疗恰加斯病的可能靶点。

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174636

Ariel Mariano Silber, Walter Colli, Henning Ulrich, Maria Júlia Manso Alves, Claudio Alejandro Pereira

{"title":"Amino acid metabolic routes in Trypanosoma cruzi: possible therapeutic targets against Chagas' disease.","authors":"Ariel Mariano Silber, Walter Colli, Henning Ulrich, Maria Júlia Manso Alves, Claudio Alejandro Pereira","doi":"10.2174/1568005053174636","DOIUrl":"https://doi.org/10.2174/1568005053174636","url":null,"abstract":"Chagas' disease is a zoonosis caused by the parasite Trypanosoma cruzi, a haematic protozoan, transmitted by insects from the Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with 11 - 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two drugs, nifurtimox and benznidazole, that were discovered more than thirty years ago, and are mainly successful during the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on patients. Trypanosoma cruzi has a metabolism largely based on the consumption of amino acids, mainly proline, aspartate and glutamate, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle. These amino acids also participate in the differentiation process of the replicative non-infective form (epimastigote) to the non-replicative infective form (trypomastigote). In particular, the participation of proline in the intracellular differentiation cycle, which occurs in the mammalian host, was recently demonstrated. In addition, an arginine kinase has been described in T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic drugs.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 1","pages":"53-64"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005053174636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25014226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 89

Blood-brain barrier drug discovery for central nervous system infections. 治疗中枢神经系统感染的血脑屏障药物的发现。

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174672

Ambrose Jong, Sheng-He Huang

{"title":"Blood-brain barrier drug discovery for central nervous system infections.","authors":"Ambrose Jong, Sheng-He Huang","doi":"10.2174/1568005053174672","DOIUrl":"https://doi.org/10.2174/1568005053174672","url":null,"abstract":"Central nervous system (CNS) infections are formidable diseases with high rates of morbidity and mortality. Since the majority of antimicrobial agents discovered so far do not cross the blood-brain barrier (BBB), the treatment of CNS infections is a major challenge issue. The development of drugs to treat those diseases requires consideration of achievable brain concentrations by targeting the following question. How can the chemistry and biology of the BBB, and infectomics be exploited for the development of drugs against CNS infections? To date drug targeting approaches, such as chemistry-based, biology-based, and infectomics-based, have been implicated in the development of drugs for treatment of CNS infections. The chemistry-based strategies rely on lipid-mediated BBB drug transport as substances that readily permeate the BBB. These usually include small molecular weight of lipophilic or hydrophobic molecules. The biology-based strategies depend on endogenous BBB transport systems, including carrier-mediated transport (CMT), active efflux transport (AET), and receptor-mediated transport (RMT). These transporters play important roles in the influxes and/or effluxes of drugs including antimicrobial agents in brain capillary endothelial cells that form the BBB. Both microbial and host signatures of infectomes, which can be dissected by infectomics, provide invaluable fountains in the search for novel antimicrobial therapies. Key markers associated with the mechanisms of neuronal injury may be identified, and thus, provide important targets for the prevention and treatment of CNS infections. This review focuses on the major BBB drug targeting strategies in the development of therapeutics for CNS infections. A combination of these strategies will ultimately lead to improved treatments.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 1","pages":"65-72"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005053174672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25014227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 34

Orthopoxvirus targets for the development of antiviral therapies. 正痘病毒是开发抗病毒疗法的目标。

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174627

Mark N Prichard, Earl R Kern

{"title":"Orthopoxvirus targets for the development of antiviral therapies.","authors":"Mark N Prichard, Earl R Kern","doi":"10.2174/1568005053174627","DOIUrl":"10.2174/1568005053174627","url":null,"abstract":"The potential use of smallpox virus as a bioterror agent and the endemic presence of monkeypox virus in Africa underscores the need for better therapies for orthopoxvirus infections. The only existing clinical experience treating vaccinia and smallpox infections has been with Marboran, which suggested that antiviral therapies could be effective in treating and preventing smallpox infections, but this compound has not been pursued. Drugs that have been approved for other indications, like cidofovir, could be approved for the treatment of orthopoxvirus infections in a timely manner, and this compound has already been approved for emergency treatment of smallpox and complications from vaccination. Its lack of activity when given orally, however, limits its use in a major outbreak involving large numbers of people exposed to the virus. The discovery and development of new therapies can be achieved more rapidly by drawing on the experience and successes with other antiviral agents, particularly with the herpesviruses. This review will discuss the orthopoxvirus replication cycle in detail noting specific viral functions and their associated gene products that have the potential to serve as new targets for drug design and development. This discussion is designed to help investigators relate these targets to parallel functions and existing assays in other virus systems that have been used successfully in drug development. The rapid progress that has been achieved in recent years should yield new drugs for the treatment of these infections and might also reveal new strategies for antiviral therapy with other viruses.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 1","pages":"17-28"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264105/pdf/nihms29069.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25014858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-targeting the entrance door to block HIV-1. 多靶点阻断HIV-1的大门。

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174645

G Borkow, A Lapidot

引用次数: 40

Advances on cyclin-dependent kinases (CDKs) as novel targets for antiviral drugs. 细胞周期蛋白依赖性激酶(CDKs)作为抗病毒药物新靶点的研究进展

Current drug targets. Infectious disorders Pub Date : 2005-03-01 DOI: 10.2174/1568005053174609

L M Schang

{"title":"Advances on cyclin-dependent kinases (CDKs) as novel targets for antiviral drugs.","authors":"L M Schang","doi":"10.2174/1568005053174609","DOIUrl":"https://doi.org/10.2174/1568005053174609","url":null,"abstract":"Although targeting viral proteins has lead to many successful antiviral drugs, these antivirals have certain limitations. They rapidly select for resistance, tend to be active against only a few related viruses and the proteins of a pathogen must be characterized before such drugs can be developed. Consequently, a long period is required from the identification of a new pathogen to the development of relevant antivirals, a major concern for emerging diseases. Cellular proteins are now considered as potential targets for antivirals. Drugs that target cellular proteins required for several viral functions might not easily select for drug-resistance. They may also be active against a variety of unrelated viruses, which commonly require the same cellular proteins, and against viral strains resistant to conventional antiviral drugs. These antivirals could be promptly tested against emerging viruses because even distantly related viruses commonly require the same cellular proteins. Cellular cyclin-dependent kinases (CDKs) are required for replication of many viruses and specific pharmacological CDK inhibitors (PCIs) are proving to have surprisingly few negative side effects in clinical trials (against cancer). PCIs inhibit replication of wild-type and multi-drug resistant strains of HIV, HSV-1, HSV-2, HCMV, EBV and VZV. Two PCIs, roscovitine and flavopiridol, were recently proven active in a mouse model of HIV-induced nephropathy. Because the antiviral mechanisms of PCIs require no viral proteins, mutations in viral genes may not easily overcome inhibition by these drugs. In fact, no PCI-resistant viral mutant has been reported. PCIs are scheduled to enter clinical trials as antivirals in 2005.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"5 1","pages":"29-37"},"PeriodicalIF":0.0,"publicationDate":"2005-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005053174609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25014856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 40