Current drug targets. Infectious disorders最新文献_第8页

Molecular targets for papillomavirus therapy. 乳头瘤病毒治疗的分子靶点。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481105

V G Wilson, G Rosas-Acosta

{"title":"Molecular targets for papillomavirus therapy.","authors":"V G Wilson, G Rosas-Acosta","doi":"10.2174/1568005033481105","DOIUrl":"https://doi.org/10.2174/1568005033481105","url":null,"abstract":"Papillomaviruses are infectious agents for human and animal epithelial tissue, and nearly 100 distinct human types (HPVs) have been identified. When these viruses infect cutaneous or mucosal skin they can initially cause clinical warts or persistent infection with little or no visible manifestations. Warts, while usually benign, can be painful or cosmetically unacceptable and often require medical treatment. Furthermore, infection with certain specific HPV types, such as 16 or 18 (as well as several others), is the major risk factor for a woman's development of cervical cancer. In addition to cervical cancer, papillomaviruses have also been implicated in cancers of the skin and respiratory track though the evidence is not yet as conclusive. It is clear that prevention or elimination of papillomavirus infections would ultimately reduce the incidence of cervical cancer and possibly other epithelial cancers as well. Unfortunately, progress in vaccine development has been slow and no specific anti-papillomavirus agents are available. The rational development of effective anti-papillomaviral treatments will require a detailed understanding of how these viruses replicate and interact with the host cell, and much progress has been made in this area over the last 10 years. These viruses have small DNA genomes with limited coding capacity, and their complete array of viral protein products is known. This review will discuss the known functions of the viral proteins with a focus on strategies to interdict their biological activities as a possible means of specific therapy.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"221-39"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015165","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: 11

Exploiting new potential targets for anti-hepatitis B virus drugs. 开发抗乙型肝炎病毒药物的新潜在靶点。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481141

Y-M Wen, X Lin, Z-M Ma

{"title":"Exploiting new potential targets for anti-hepatitis B virus drugs.","authors":"Y-M Wen, X Lin, Z-M Ma","doi":"10.2174/1568005033481141","DOIUrl":"https://doi.org/10.2174/1568005033481141","url":null,"abstract":"Based on the recent studies of HBV strains with different replication efficiency, several new potential targets for anti-HBV replication have been presented. These include the viral and cellular regulatory factors associated with HBV replication and the process for encapsidation of viral genome and budding into endoplasmic reticulum (ER). A putative regulatory domain has been reported at the carboxyl-end of reverse transcriptase (RT) and when serine is substituted for proline at residue 652 of RT, replication efficiency of HBV is decreased. Substitution of proline for threonine at the 2798 nucleotide of the terminal protein (TP) gene, renders the mutant completely replication deficient. Expression of TP blocks the interferon (IFN) pathway and inhibits the responsive state of cells to interferons ( IFN) alpha and gamma. Interference of HBV capsid assembly drastically affects the encapsidation of viral genome, a crucial process for reverse transcription and viral DNA synthesis. Small molecules (bis-ANS) have been reported to act as a \"wedge\" to misdirect the polymerization of capsid, resulting in inhibition of virus replication. Another new group of compounds (HAP) has been shown to inhibit virus replication and also inhibit the assembly of viral capsid (core particle). Finally the capsids containing HBV genome are enveloped by budding into endoplasmic reticulum and release from virus infected cells, and this morphogenesis and secretion of HBV is dependent on glucosidases in the ER of host cells. Competitive inhibition of these glucosidases has been suggested as strategy against HBV replication.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"241-6"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015166","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: 18

Vaccine development for potential bioterrorism agents. 开发潜在生物恐怖主义制剂的疫苗。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481097

R W Titball, E D Williamson

{"title":"Vaccine development for potential bioterrorism agents.","authors":"R W Titball, E D Williamson","doi":"10.2174/1568005033481097","DOIUrl":"https://doi.org/10.2174/1568005033481097","url":null,"abstract":"Vaccines are considered to be one of the most effective ways of combating disease caused by bioterrorism agents. Such vaccines must be able to provide protection against pathogens which might enter the body by a number of routes, including the respiratory tract. They should also be able to induce protective immunity rapidly and would ideally be given non-invasively. There are few vaccines which currently meet these requirements. In part, this reflects the low level of research on many bioterrorism agents over the past few decades. Little is known about basic mechanisms of pathogenicity of many of these agents. However, by their very nature these agents cause serious disease, and must be handled in high containment laboratories. This requirement also limits the speed and ease with which research on these pathogens can now take place. Against this background, research on vaccines against potential bioterrorism agents is likely to proceed along two lines. Firstly because the genome sequences of most of the principal bioterrorism agents have either been completed or are close to completion, there is likely to be reliance on the exploitation of this information to devise improved vaccines. A number of groups are working on methodologies to identify vaccine antigens directly from genome sequences. Secondly, there will be a need to formulate such vaccines appropriately for the rapid induction of protective immunity after non-invasive delivery. The prospects for the development of a new generation of bioterrorism vaccines which exploit these technologies are reviewed in this manuscript.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"255-62"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015168","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: 13

Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. 牛痘载体作为候选疫苗:用于抗原递送的修饰型安卡拉牛痘病毒的研制。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481123

Gerd Sutter, Caroline Staib

{"title":"Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery.","authors":"Gerd Sutter, Caroline Staib","doi":"10.2174/1568005033481123","DOIUrl":"https://doi.org/10.2174/1568005033481123","url":null,"abstract":"Vaccinia viruses engineered to express foreign genes are powerful vectors for production of recombinant proteins. Originating from highly efficacious vaccines securing world-wide eradication of smallpox, the most appealing use of vaccinia vectors is to serve as vaccine delivery system for heterologous antigens. Concerns about the safety of vaccinia virus have been addressed by the development of vectors based on attenuated viruses. One of them, modified vaccinia virus Ankara (MVA) can be considered as current vaccinia virus strain of choice for clinical investigation. Historical development and use of MVA as vaccine against smallpox allowed to establish an extraordinary safety profile. MVA can be used under conditions of biosafety level 1 because of its avirulence and its deficiency to productively grow in human cells. In recent years significant progress has been made with regard to the development of MVA vector technologies. Compared to replication competent vaccinia viruses, MVA provides similar levels of recombinant gene expression even in nonpermissive cells. In animal models, MVA vaccines have been found immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza, parainfluenza, measles virus, flaviviruses, or plasmodium parasites. By now first data from clinical trials are becoming available. In this article we briefly review history of MVA and state-of-the art technologies with regard to generation of recombinant MVA vaccines, and describe the progress to develop MVA vector vaccines against important infectious diseases.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"263-71"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568005033481123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015169","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: 194

Targeting NS5B RNA-dependent RNA polymerase for anti-HCV chemotherapy. 靶向NS5B RNA依赖RNA聚合酶的抗hcv化疗。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481114

Jim Zhen Wu, Zhi Hong

{"title":"Targeting NS5B RNA-dependent RNA polymerase for anti-HCV chemotherapy.","authors":"Jim Zhen Wu, Zhi Hong","doi":"10.2174/1568005033481114","DOIUrl":"https://doi.org/10.2174/1568005033481114","url":null,"abstract":"The global prevalence of persistent hepatitis C virus (HCV) infection and the lack of a highly effective and well-tolerated antiviral therapy have spurred intensive efforts to discover and develop novel anti-HCV therapy in the pharmaceutical industry. HCV NS5B RNA-dependent RNA polymerase (RdRp), the centerpiece for viral replication, constitutes a valid target for drug discovery. Compared to the host RNA and DNA polymerases, NS5B RdRp has distinct subcellular localization at the interface of the endoplasmic reticulum (ER) membrane and cytoplasm, a novel catalytic mechanism and many unique structural features, all of which make it an attractive target for developing effective anti-HCV therapeutics. High genetic variation among the major HCV genotypes commands that any efficacious NS5B inhibitors have to be broadly active against NS5Bs from various genotypes. Rapid viral replication and its inherent genetic diversity will certainly culminate drug resistance to any NS5B inhibitors. Therefore, iterative drug design and combination therapies of drugs that intervene with different steps in the HCV replicative cycle are needed to combat the viral infection. Many classes of nucleoside and non-nucleoside inhibitors of NS5B RdRp have been identified and appeared in literatures and patent applications. These progresses hold a considerable promise to the development of novel, specific and highly effective therapeutics to achieve sustained response and ultimately the eradication of HCV infection.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"207-19"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015265","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: 37

Current and future therapy for chronic hepatitis C virus liver disease. 慢性丙型肝炎病毒肝病的当前和未来治疗。

Current drug targets. Infectious disorders Pub Date : 2003-09-01 DOI: 10.2174/1568005033481132

G Lake-Bakaar

{"title":"Current and future therapy for chronic hepatitis C virus liver disease.","authors":"G Lake-Bakaar","doi":"10.2174/1568005033481132","DOIUrl":"https://doi.org/10.2174/1568005033481132","url":null,"abstract":"Therapy with recombinant human interferon alpha remains pivotal to the treatment for chronic hepatitis C virus liver disease. Semi-synthetic protein-polymer conjugates of interferon with polyethylene glycol have also been recently developed. These conjugates protect the protein from degradation; reduce the immunogenicity; and prolong exposure to drug by a sustained absorption, restricted volume of distribution and sustained high serum concentration. Therapy with pegylated interferons is associated with significantly greater sustained virological response rates (SVR) compared to the non-pegylated formulation. Ribavirin is a guanosine analog with minimal antiviral activity against HCV. It demonstrates significant clinical synergism when administered in combination with interferon. Amantadine blocks entry of influenza A virus into cells. Used in combination with ribavirin and interferon as triple therapy, it may have some benefit compared to dual or monotherapy. Current treatment with pegylated interferons combined with weight-based ribavirin, provides the highest sustained virological response rates. In the absence of suitable animal models, HCV dynamic studies in man have been helpful in defining the mechanisms of action of interferon in chronic HCV liver disease. Novel therapeutic agents are being developed as the replication cycle of HCV is being understood. However, their safety and efficacy remain to be established and availability for clinical use is unlikely within the next 3 to 5 years. This review describes current antiviral therapy in chronic HCV liver disease, addresses the potential role of viral dynamics in elucidating the mechanisms of action of the drugs and discusses future potential therapeutics agents.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 3","pages":"247-53"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24015167","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: 23

Immunological approaches for HIV therapy. HIV治疗的免疫学方法。

Current drug targets. Infectious disorders Pub Date : 2003-06-01 DOI: 10.2174/1568005033481204

F Lori, L M Kelly, J Lisziewicz

{"title":"Immunological approaches for HIV therapy.","authors":"F Lori, L M Kelly, J Lisziewicz","doi":"10.2174/1568005033481204","DOIUrl":"https://doi.org/10.2174/1568005033481204","url":null,"abstract":"The induction of a Th-1 polarized immune response is believed to be advantageous when designing immunologic approaches for HIV therapy. DNA vaccines represent one of the best immunologic strategies capable of inducing such a response. From conception to clinical application it is now possible to rationally design DNA vaccines based on reliable experimental data, thus a systemic approach to the development of new and the enhancement of existing vaccine immunogens is now possible. The addition of adjuvants may also increase immunogenicity and depending on the choice of adjuvant, polarize the immune response. Other important factors in the formulation of a successful vaccine are the selection of administration route, heterologous or homologous prime/boost schedules, and the feasibility of the eventual clinical application. This review will summarize recently developed preventive and therapeutic vaccines, and carefully evaluate the advantages and potential risks for Human Immunodeficiency Virus (HIV) infected patients. Finally, the concept of \"autovaccination\" will be defined as it represents the basis for the development of our innovative therapeutic antigen presenting cell targeted HIV vaccine. DermaVir is the first topical vaccine, in combination with antiretroviral therapy, to demonstrate immunological and clinical benefits in a relevant animal model (chronically infected rhesus macaques).","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 2","pages":"171-8"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22404860","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: 5

Current perspectives on cytokines for anti-retroviral therapy in AIDS related B-cell lymphomas. 细胞因子在艾滋病相关b细胞淋巴瘤抗逆转录病毒治疗中的应用现状

Current drug targets. Infectious disorders Pub Date : 2003-06-01 DOI: 10.2174/1568005033481178

V Sharma

{"title":"Current perspectives on cytokines for anti-retroviral therapy in AIDS related B-cell lymphomas.","authors":"V Sharma","doi":"10.2174/1568005033481178","DOIUrl":"https://doi.org/10.2174/1568005033481178","url":null,"abstract":"The development of high-grade B-cell lymphoma in Acquired Immunodeficiency Syndrome (AIDS) patients is a relatively late manifestation induced by Human Immunodeficiency Virus-1 (HIV) infection and is considered to be an AIDS-defining condition. Multiple, ongoing molecular and cytogenetic aberrations appear necessary for the development of AIDS-related lymphoma. Studying a panel of human B-cell lines derived from patients with Burkitt's lymphoma (BL) and AIDS-associated Burkitt's lymphoma (AIDS-BL) we had described constitutive expression and secretion of large amounts of Interleukin-16 (IL-16), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), Macrophage Inflammatory Protein-1beta (MIP-1beta), Interleukin-12 (IL-12), Interleukin-10 (IL-10), and Interleukin-7 (IL-7). Some of these cytokines like IL-16, MIP-1beta, MIP-1alpha and Regulated upon activation normal T expressed and secreted (RANTES) are shown to have inhibitory effect on HIV replication. Interestingly, we identified a novel transcription factor family, Macrophage Inflammatory Protein-1alpha Nuclear Protein (MNP), which is suggested as a potential target for anti-retroviral therapy based on the implication of its role and involvement as a key regulator of MIP-1alpha. It is apparent, that HIV induces the production of a cascade of cytokines and cytokine receptors. Some of these molecules serve to increase the infection and replication of HIV per se, and some others serve to induce a state of B-cell growth, activation, and differentiation. This review attempts to delineate the complex mechanisms of viral, B-cell, oncogene, cytokine/cytokine receptor and transcription factor interactions that are involved in AIDS associated lymphomagenesis. Unfolding the relationship between cytokines and the underlying mechanisms of the disease will not only help in understanding the pathophysiology but also will facilitate focusing on the development of new diagnostic and therapeutic strategies.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 2","pages":"137-49"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22404858","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: 11

Viral reservoirs an impediment to HAART: new strategies to eliminate HIV-1. 病毒储存库是HAART的障碍:消除HIV-1的新策略。

Current drug targets. Infectious disorders Pub Date : 2003-06-01 DOI: 10.2174/1568005033481187

Nitin K Saksena, Da'ed N Haddad

引用次数: 20

Viral latent proteins as targets for Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) induced lymphoma. 病毒潜伏蛋白作为卡波西肉瘤和卡波西肉瘤相关疱疹病毒(KSHV/HHV-8)诱导淋巴瘤的靶点

Current drug targets. Infectious disorders Pub Date : 2003-06-01 DOI: 10.2174/1568005033481150

Michelle R Staudt, Dirk P Dittmer

{"title":"Viral latent proteins as targets for Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) induced lymphoma.","authors":"Michelle R Staudt, Dirk P Dittmer","doi":"10.2174/1568005033481150","DOIUrl":"https://doi.org/10.2174/1568005033481150","url":null,"abstract":"Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is present in all Kaposi's sarcoma tumor cells as well as in several lymphomas that are linked to this agent. Every tumor cell expresses the viral latent protein LANA, which is required for KSHV latent replication and proper segregation of the viral episome. In certain tumors, other latent KSHV proteins (LANA-2/vIRF3, v-cyclin, v-IL6) are expressed as well. Since all herpesviruses persist for life in infected individuals, only eradication of latent virus can cure infection. The KSHV latent genes serve as bona fide tumor markers, but do they also provide targets for anti-tumor and/or anti-viral drugs? To decide this question we review the known biochemical interactions between KSHV latent proteins and their viral and cellular partners. Recent epidemiological studies show that KSHV lytic replication precedes KSHV associated cancers. Gancilovir has been linked to KS tumor regression, which implicates the KSHV-encoded polymerase as a potential intervention point. Yet, KSHV specific transactivators might represent more specific targets, as they have no cellular homologs. In particular Rta/orf50 is necessary and sufficient for lytic replication and deserves serious consideration as a target for KSHV-specific antivirals.","PeriodicalId":84525,"journal":{"name":"Current drug targets. Infectious disorders","volume":"3 2","pages":"129-35"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22404857","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: 20