The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Donald P Mcmanus - One of the best experts on this subject based on the ideXlab platform.
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Protease Inhibitors of Parasitic Flukes: Emerging Roles in Parasite Survival and Immune Defence.
Trends in parasitology, 2017Co-Authors: Shiwanthi L. Ranasinghe, Donald P McmanusAbstract:Protease Inhibitors play crucial roles in parasite development and survival, counteracting the potentially damaging immune responses of their vertebrate hosts. However, limited information is currently available on Protease Inhibitors from schistosomes and food-borne trematodes. Future characterization of these molecules is important not only to expand knowledge on parasitic fluke biology but also to determine whether they represent novel vaccine and/or drug targets. Moreover, Protease Inhibitors from flukes may represent lead compounds for the development of a new range of therapeutic agents against inflammatory disorders and cancer. This review discusses already identified Protease Inhibitors of fluke origin, emphasizing their biological function and their possible future development as new intervention targets.
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Serine Protease Inhibitors of parasitic helminths.
Parasitology, 2012Co-Authors: Adebayo J. Molehin, Geoffrey N. Gobert, Donald P McmanusAbstract:Serine Protease Inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine Proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine Protease Inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.
Lars Berglund - One of the best experts on this subject based on the ideXlab platform.
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HIV Protease Inhibitors and obesity.
Current Opinion in Endocrinology Diabetes and Obesity, 2010Co-Authors: Erdembileg Anuurad, Andrew A. Bremer, Lars BerglundAbstract:Purpose of review To review the current scientific literature and recent clinical trials on HIV Protease Inhibitors (PIs) and their potential role in the pathogenesis of lipodystrophy and metabolic disorders.
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HIV Protease Inhibitors and obesity.
Current opinion in endocrinology diabetes and obesity, 2010Co-Authors: Erdembileg Anuurad, Andrew A. Bremer, Lars BerglundAbstract:Purpose of review To review the current scientific literature and recent clinical trials on HIV Protease Inhibitors and their potential role in the pathogenesis of lipodystrophy and metabolic disorders. Recent findings HIV Protease inhibitor treatment may affect the normal stimulatory effect of insulin on glucose and fat storage. Further, chronic inflammation from HIV infection and Protease inhibitor treatment trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. This process leads to a pathologic cycle of lipodystrophy and lipotoxicity, a proatherogenic lipid profile, and a clinical phenotype of increased central body fat distribution similar to the metabolic syndrome. Summary Protease Inhibitors are a key component of antiretroviral therapy and have dramatically improved the life expectancy of HIV-infected individuals. However, they are also associated with abnormalities in glucose/lipid metabolism and body fat distribution. Further studies are needed to better define the pathogenesis of Protease inhibitor-associated metabolic and body fat changes and their potential treatment.
Ronald Swanstrom - One of the best experts on this subject based on the ideXlab platform.
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Viral Protease Inhibitors.
Handbook of experimental pharmacology, 2009Co-Authors: Jeffrey A. Anderson, Celia A. Schiffer, Sook-kyung Lee, Ronald SwanstromAbstract:This review provides an overview of the development of viral Protease Inhibitors as antiviral drugs. We concentrate on HIV-1 Protease Inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 Protease, inhibitor development, clinical use of Inhibitors, and evolution of resistance. Since many different viruses encode essential Proteases, it is possible to envision the development of a potent Protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing Inhibitors is limited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufficiently ubiquitous that treating an acute infection would be beneficial even if the infection was ultimately self-limiting. Protease inhibitor development is most advanced for hepatitis C virus (HCV), and we also provide a review of HCV NS3/4A serine Protease inhibitor development, including combination therapy and resistance. Finally, we discuss other viral Proteases as potential drug targets, including those from Dengue virus, cytomegalovirus, rhinovirus, and coronavirus.
Kiran Babu Uppuluri - One of the best experts on this subject based on the ideXlab platform.
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Microbial serine Protease Inhibitors and their therapeutic applications.
International Journal of Biological Macromolecules, 2017Co-Authors: B.s. Harish, Kiran Babu UppuluriAbstract:Abstract Serine Protease Inhibitors, inhibit serine Proteases either partially or completely after forming complexes with their respective Proteases. Protease actions are significant for many physiological pathways found in living forms and any anomalies may lead to numerous physiological complications. Each cell or organism has its own mechanism for controlling these Protease actions. It is often regulated by the action of Inhibitors or activators. Among the Proteases, serine Proteases are the most common that are involved in many life and death processes. Selective Inhibitors of physiologically relevant Proteases can be used as a lead compound for the drug development. Therefore, it is imperative to identify small peptides and proteins that selectively inhibit serine Proteases from various sources. Microbes can be considered as a major source of diverse serine Protease Inhibitors since they have the prominent and diverse domain in nature. Most of the microbial serine Protease Inhibitors are intracellular and few are extracellular. Microbes produce Protease Inhibitors for protection against its own Proteases or against other environmental factors. The status and future prospects of microbial serine Protease Inhibitors and their therapeutic benefits in treating cancer, blood coagulation disorders and viral infections, are reviewed here.
Joseph A. Paladino - One of the best experts on this subject based on the ideXlab platform.
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Protease Inhibitors for Hepatitis C: Economic Implications
PharmacoEconomics, 2013Co-Authors: Stuart J. Turner, Jack Brown, Joseph A. PaladinoAbstract:Chronic hepatitis C virus (HCV) infection, a blood-borne virus, is the leading cause of chronic liver disease and liver transplantation worldwide. Chronic HCV infection is usually asymptomatic in the early stages of the disease, making an estimation of the total population affected difficult to elicit. The gold standard treatment option to date has been a combination of pegylated interferon and ribavirin. Recent developments have led to the introduction of two Protease Inhibitors for use in chronic HCV—boceprevir and telaprevir. Phase III studies have shown both agents have the potential to significantly increase the probability of attaining a sustained virologic response (the primary outcome of interest in chronic HCV) in genotype 1 infections. However, the added cost of these agents also presents the need for decision makers to determine their place on drug formularies. The Protease Inhibitors are to be administered as triple therapy with the existing gold standard. However, significant variation exists as to the proposed duration of triple therapy, use of lead-in pegylated interferon and ribavirin and subsequent pegylated interferon therapy after finishing the course of triple therapy. Treatment algorithms also exist for the use of stopping rules in the case of early non-responders. The aim of this review is to highlight the current understanding of the economic impact Protease Inhibitors may have on health care systems and considerations required in the treatment of HCV. Economic and health-related quality of life issues are addressed from multiple viewpoints. The major aspects of the economic evaluations, to date, that included triple therapy as an alternative in the treatment of chronic HCV are brought to light. Future economic evaluations in alternative settings would be useful. The review also emphasizes the challenges for future research. This includes the potential for new therapies to no longer require inclusion of pegylated interferon and/or ribavirin, as well as the use of Protease Inhibitors in non-genotype 1 patients or those with significant co-morbidities such as HIV/AIDS.
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Protease Inhibitors for Hepatitis C: Economic Implications
PharmacoEconomics, 2013Co-Authors: Stuart J. Turner, Jack Brown, Joseph A. PaladinoAbstract:Chronic hepatitis C virus (HCV) infection, a blood-borne virus, is the leading cause of chronic liver disease and liver transplantation worldwide. Chronic HCV infection is usually asymptomatic in the early stages of the disease, making an estimation of the total population affected difficult to elicit. The gold standard treatment option to date has been a combination of pegylated interferon and ribavirin. Recent developments have led to the introduction of two Protease Inhibitors for use in chronic HCV—boceprevir and telaprevir. Phase III studies have shown both agents have the potential to significantly increase the probability of attaining a sustained virologic response (the primary outcome of interest in chronic HCV) in genotype 1 infections. However, the added cost of these agents also presents the need for decision makers to determine their place on drug formularies. The Protease Inhibitors are to be administered as triple therapy with the existing gold standard. However, significant variation exists as to the proposed duration of triple therapy, use of lead-in pegylated interferon and ribavirin and subsequent pegylated interferon therapy after finishing the course of triple therapy. Treatment algorithms also exist for the use of stopping rules in the case of early non-responders. The aim of this review is to highlight the current understanding of the economic impact Protease Inhibitors may have on health care systems and considerations required in the treatment of HCV. Economic and health-related quality of life issues are addressed from multiple viewpoints. The major aspects of the economic evaluations, to date, that included triple therapy as an alternative in the treatment of chronic HCV are brought to light. Future economic evaluations in alternative settings would be useful. The review also emphasizes the challenges for future research. This includes the potential for new therapies to no longer require inclusion of pegylated interferon and/or ribavirin, as well as the use of Protease Inhibitors in non-genotype 1 patients or those with significant co-morbidities such as HIV/AIDS.
