Gene/Protein Disease Symptom Drug Enzyme Compound
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Entry of SARS-CoV into a target cell is initiated by binding of the S1 domain of spike protein to a receptor, followed by conformational changes of the spike protein S2 domain, resulting in the formation of a six-helix bundle by the heptad-repeat (HR1 and HR2) regions. Our previous studies have demonstrated that peptides derived from HR2 region could inhibit SARS-CoV entry. However, synthesis of these peptides is at high cost. In this study, we designed two recombinant proteins, one containing two HR1 and one HR2 peptides (denoted HR121), and the other consisting of two HR2 and one HR1 peptides (designated HR212). These two proteins could be easily purified with the low cost of production, exhibiting high stability and potent inhibitory activity on entry of the HIV/SARS pseudoviruses with IC(50) values of 4.13 and 0.95muM, respectively. These features suggest that HR121 and HR212 can serve as potent inhibitors of SARS-CoV entry.
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PMID:Design of recombinant protein-based SARS-CoV entry inhibitors targeting the heptad-repeat regions of the spike protein S2 domain. 1578 Dec 29

Prevention has been the greatest success in the field of infectious diseases. Control of infectious diseases is being challenged by many factors, like standards of living, human behaviour, mass population movements, emergence of infectious like HIV/AIDS and SARS, the re-emergence of infections such as tuberculosis, development of resistance in bacteria, viruses and parasites, modern rate of global travel, etc. Although great advances have been made, a considerable burden of morbidity and mortality from infectious diseases remains globally. The aim of any control program can be defined by three levels--containment, elimination and eradication. Prevention methods are many aspects, including introduction of prevention guidelines, low cost interventions, vector control, surveillance, and vaccination, etc.
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PMID:[Global strategies in prevention of infectious diseases on the turn of the second and third millennium: expectation versus reality]. 1580 51

Preventive vaccines are widely acknowledged as the best hope for protection against infectious pathogens such as avian flu, HIV and SARS. As a result, they have received much recent attention in the media that has exposed some of the challenges involved in optimally using vaccine technology.
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PMID:Vaccines in the public eye. 1581 85

Since the emergence of HIV/AIDS in the 1980s, social scientists and sociologists of health and illness have been exploring the metaphorical framing of this infectious disease in its social context. Many have focused on the militaristic language used to report and explain this illness, a type of language that has permeated discourses of immunology, bacteriology and infection for at least a century. In this article, we examine how language and metaphor were used in the UK media's coverage of another previously unknown and severe infectious disease: Severe Acute Respiratory Syndrome (SARS). SARS offers an opportunity to explore the cultural framing of a less extraordinary epidemic disease. It therefore provides an analytical counter-weight to the very extensive body of interpretation that has developed around HIV/AIDS. By analysing the total reporting on SARS of five major national newspapers during the epidemic of spring 2003, we investigate how the reporting of SARS in the UK press was framed, and how this related to media, public and governmental responses to the disease. We found that, surprisingly, militaristic language was largely absent, as was the judgemental discourse of plague. Rather, the main conceptual metaphor used was SARS as a killer. SARS as a killer was a single unified entity, not an army or force. We provide some tentative explanations for this shift in linguistic framing by relating it to local political concerns, media cultures, and spatial factors.
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PMID:Disease metaphors in new epidemics: the UK media framing of the 2003 SARS epidemic. 1581 87

In June 2001, the American Medical Association (AMA) issued a revised and expanded version of the Principles of Medical Ethics (last published in 1980). In light of the new and more comprehensive document, the present essay is geared to consideration of a longstanding tension between physician's autonomy rights and societal obligations in the AMA Code. In particular, it will be argued that a duty to treat overrides AMA autonomy rights in social emergencies, even in cases that involve personal risk to physicians (e.g., bioterrorist attack, HIV infection, SARS). The argument will be made by way of the logic and language of the AMA Code through its history, commentaries, and precedents. It also will be shown that there are substantial reasons to believe that the logic of the Code is sound in morally relevant ways. The essay will conclude with some philosophical proposals suggesting a framework for the duty to render aid and the extension of those duties to physicians facing personal risks.
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PMID:In harm's way: AMA physicians and the duty to treat. 1581 68

The importance of infections for public health has become obvious during the last decades. Examples are emerging infections such as HIV/AIDS and severe acute respiratory syndrome, deliberate release of microorganisms, such as the anthrax episode in the USA, the increasing problems with organisms resistant to antimicrobial treatment, such as methicillin-resistant Staphylococcus aureus, and the threat of a new influenza pandemic with a case fatality rate similar to that in the 1918 outbreak. An effective response to infectious disease emergencies requires careful planning and establishment of resources in advance. The medical specialties involved are clinical microbiology, clinical infectious diseases and epidemiology. Clinical microbiology should include bacteriology, virology, and parasitology; the technical developments during the last 15 years have clearly erased most of the methodological differences between these branches of microbiology. New techniques such as new generations of Polymerase Chain Reaction (PCR), rapid methods for nucleic acid sequence analyses and microarrays have enabled more rapid identification of organisms and provide powerful tools in the epidemiological analysis of an outbreak. The infectious disease specialists are necessary for rapid and adequate clinical diagnoses, optimal use of antimicrobial agents and provision of facilities for containment of patients who may spread the infections. The need for isolation units became acute when many countries prepared themselves for a possible severe acute respiratory syndrome outbreak in Europe. With few exceptions, Europe still lacks epidemiological field forces, and it has been embarrassing to be obliged to call upon the Centers for Disease Control for European outbreaks. Hopefully, this will be corrected with the creation of the European Centre for Disease Prevention and Control (ECDC).
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PMID:Infectious disease emergencies: role of the infectious disease specialist. 1581

Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), reemerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have contributed substantially to this effort. This overview highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed.
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PMID:Emerging infectious diseases: a 10-year perspective from the National Institute of Allergy and Infectious Diseases. 1582 88

We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.
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PMID:rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens. 1583 68

The RNA-dependent RNA polymerase (RdRp) of SARS coronavirus (SARS-CoV) is essential for viral replication and a potential target for anti-SARS drugs. We report here the cloning, expression, and purification of the N-terminal GST-fused SARS-CoV RdRp and its polymerase catalytic domain in Escherichia coli. During purification, the full-length GST-RdRp was found to cleave into three main fragments: an N-terminal p12 fragment, a middle p30 fragment, and a C-terminal p64 fragment comprising the catalytic domain, presumably due to bacterial proteases. Biochemical assays show that the full-length GST-RdRp has RdRp activity and the p64 and p12 fragments form a complex that exhibits comparable RdRp activity, whereas the GST-p64 protein has no activity, suggesting that the p12 domain is required for polymerase activity possibly via involvement in template-primer binding. Nonnucleoside HIV-1 RT inhibitors are shown to have no evident inhibitory effect on SARS-CoV RdRp activity. This work provides a basis for biochemical and structural studies of SARS-CoV RdRp and for development of anti-SARS drugs.
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PMID:Expression, purification, and characterization of SARS coronavirus RNA polymerase. 1584 May 16

Lipopeptide lipid moieties induce dendritic cell (DC) internalization and epitopes are recognized by MHC, the major histocompatibility complex. HIV-1 (human immunodeficiency virus type 1) lipopeptide vaccine candidate elicits immune responses, and sustains HIV control after highly active antiretroviral therapy (HAART). Mp- and Dp-MART (anti-melanoma lipopeptides) induce strong CTL (cytolytic T lymphocyte) response. New BGTC, BGDA, TGKC lipoplexes mediate gene delivery, e.g., into mouse pancreatic tumor nodules. Triterpene glycyrrhizic acid (GL) inhibits SARS-CoV (severe acute respiratory syndrome associated coronavirus) replication. Compared to CDV (cidofovir), CDV ether lipid esters have enhanced activity against vaccinia (VV) and cowpox (CV) viruses in vitro. Oral treatment of VV and CV infected mice with CDV ether lipid esters, as effective as i.p. CDV, may be useful against orthopoxvirus infections in humans.
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PMID:Development in lipid drugs. 1589 90


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