Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The capacity of the surface glycoproteins of enveloped viruses to mediate virus/cell binding and membrane fusion requires a proper thiol/disulfide balance. Chemical manipulation of their redox state using reducing agents or free sulfhydryl reagents affects virus/cell interaction. Conversely, natural thiol/disulfide rearrangements often occur during the cell interaction to trigger fusogenicity, hence the virus entry. We examined the relationship between the redox state of the 20 cysteine residues of the SARS-CoV (severe acute respiratory syndrome coronavirus) Spike glycoprotein S1 subdomain and its functional properties. Mature S1 exhibited approximately 4 unpaired cysteines, and chemically reduced S1 displaying up to approximately 6 additional unpaired cysteines still bound ACE2 and enabled fusion. In addition, virus/cell membrane fusion occurred in the presence of sulfhydryl-blocking reagents and oxidoreductase inhibitors. Thus, in contrast to various viruses including HIV (human immunodeficiency virus) examined in parallel, the functions of the SARS-CoV Spike glycoprotein exhibit a significant and surprising independence of redox state, which may contribute to the wide host range of the virus. These data suggest clues for molecularly engineering vaccine immunogens.
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PMID:Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: comparison with HIV envelope. 1641 66

New pathogens and antimicrobial-resistant forms of older pathogens continue to emerge, some with the potential for rapid, global spread and high morbidity and mortality. Pathogens can emerge either through introduction into a new population or when the interaction with the vector changes; emergence is also influenced by microbiological adaptation and change, global travel patterns, domestic and wild animal contact and other variants in human ecology and behaviour. Quick, decisive action to detect and control novel pathogens, and thereby contain outbreaks and prevent further transmission, is frequently hampered by incomplete or inadequate data about a new or re-emerging pathogen. Three examples of pathogens that are current causes for human health concern are avian influenza, West Nile virus (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens directly or indirectly transmitted by aerosolized droplets, such as avian influenza and SARS, pose considerable containment challenges. Rapid screening tests for other newly described pathogens such as WNV require time for development and may be <100% reliable. The importance of vigilance in the detection and control of newly recognized infectious threats cannot be overstressed. The presence of infectious agents in the blood supply could again have a significant impact on the safe use of both blood and blood-derived products in the care of patients with haemophilia, as did the human immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a reality requiring the collaborative efforts of public health and individual healthcare providers worldwide to contain outbreaks and prevent transmission.
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PMID:Emerging viral diseases and infectious disease risks. 1644 11

This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.
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PMID:Developments in antiviral drug design, discovery and development in 2004. 1653 60

To understand the roles of heptad repeat 1(HR1) and HR2 of the spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) in virus-cell interactions, the conserved Leu or Ile residues located at positions 913, 927, 941, and 955 in HR1 and 1151, 1165, and 1179 in HR2 were individually replaced with an alpha-helix-breaker Pro residue. The 913P mutant was expressed mainly as a faster-migrating, lower-molecular-weight S(L) form, while the wild type and all other mutants produced similar levels of both the S(L) form and the slower-migrating, higher-molecular-weight S(H) form. The wild-type S(L) form was processed to the S(H) form, whereas the S(L) form of the 913P mutant was inefficiently converted to the S(H) form after biosynthesis. None of these mutations affected cell surface expression or binding to its cognate ACE2 receptor. In a human immunodeficiency virus type 1/SARS S coexpression study, all mutants except the 913P mutant incorporated the S(H) form into the virions as effectively as did the wild-type S(H) form. The mutation at Ile-1151 did not affect membrane fusion or viral entry. The impaired viral entry of the 927P, 941P, 955P, and 1165P mutants was due to their inability to mediate membrane fusion, whereas the defect in viral entry of the 1179P mutant occurred not at the stage of membrane fusion but rather at a postfusion stage. Our study demonstrates the functional importance of HR1 and HR2 of the SARS-CoV spike protein in membrane fusion and viral entry.
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PMID:Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. 1653 90

In the age of extensive global traffic systems, the close neighborhood of man and livestock in some regions of the world, as well as inadequate prevention measures and medical care in poorer countries, greatly facilitates the emergence and dissemination of new virus strains. The appearance of avian influenza viruses that can infect humans, the spread of the severe acute respiratory syndrome (SARS) virus, and the unprecedented raging of human immunodeficiency virus (HIV) illustrate the threat of a global virus pandemic. In addition, viruses like hepatitis B and C claim more than one million lives every year for want of efficient therapy. Thus, new approaches to prevent virus propagation are urgently needed. Antisense strategies are considered a very attractive means of inhibiting viral replication, as oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The ensuing targeted destruction of viral RNA should interfere with viral replication without entailing negative effects on ongoing cellular processes. In this review, we will give some examples of the employment of antisense oligonucleotides, ribozymes, and RNA interference strategies for antiviral purposes. Currently, in spite of encouraging results in preclinical studies, only a few antisense oligonucleotides and ribozymes have turned out to be efficient antiviral compounds in clinical trials. The advent of RNA interference now seems to be refueling hopes for decisive progress in the field of therapeutic employment of antisense strategies.
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PMID:Oligonucleotide-based antiviral strategies. 1659 20

Various semisynthetic derivatives of glycopeptide antibiotics including vancomycin, eremomycin, teicoplanin, ristocetin A and DA-40926 have been evaluated for their inhibitory activity against feline infectious peritonitis virus (FIPV) and human (SARS-CoV, Frankfurt-1 strain) coronavirus in cell culture in comparison with their activity against human immunodeficiency virus (HIV). Several glycopeptide derivatives modified with hydrophobic substituents showed selective antiviral activity. For the most active compounds, the 50% effective concentrations (EC(50)) were in the lower micromolar range. In general, removal of the carbohydrate parts of the molecules did not affect the antiviral activity of the compounds. Some compounds showed inhibitory activity against both, whereas other compounds proved inhibitory to either, FIPV or SARS-CoV. There was no close correlation between the EC(50) values of the glycopeptide derivatives for FIPV or SARS-CoV.
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PMID:Inhibition of feline (FIPV) and human (SARS) coronavirus by semisynthetic derivatives of glycopeptide antibiotics. 1667 38

This study compares public stigma towards three types of infectious diseases- human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), severe acute respiratory syndrome (SARS), and tuberculosis (TB)-tests an attribution model of stigma, and explores the relationships between stigma and public attitudes towards government policies in Hong Kong. Using a population-based telephone survey, 3011 Hong Kong Chinese adults were randomly assigned to one of the three disease conditions and were interviewed about their attitudes and beliefs towards the assigned disease. Findings showed that public stigma was the highest towards HIV/AIDS, followed by TB and SARS. Using multi-sample model structural equation modeling, we found that the attributions of controllability, personal responsibility, and blame were applicable in explaining stigma across three disease types. Knowledge about the disease had no significant effect on stigma. Participants with less stigmatizing views had significantly more favorable attitudes towards government policies related to the diseases. The study is an important attempt in understanding the attributional mechanisms of stigma towards infectious diseases. Implications for stigma reduction and promotion of public awareness and disease prevention are discussed.
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PMID:Comparative stigma of HIV/AIDS, SARS, and tuberculosis in Hong Kong. 1676 6

Peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, Coronavirus 229 E, severe acute respiratory syndrome coronavirus and Ebola virus were all potent antagonists of the formyl peptide receptor expressed in Chinese hamster ovary cells. Binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. Substitution of R190 with W190 enhanced the affinity for a severe acute respiratory syndrome coronavirus peptide 6 fold but reduced the affinity for N-formyl-Nle-Leu-Phe by 2.5 fold. A 12 mer peptide derived from coronavirus 229E (ETYIKPWWVWL) was the most potent antagonist of the formyl peptide receptor W190 with a K(i) of 230 nM. Fluorescently labeled ETYIKPWWVWL was effectively internalized by all three variants with EC(50) of approximately 25 nM. An HKU-1 coronavirus peptide, MYVKWPWYVWL, was a potent antagonist but N-formyl-MYVKWPWYVWL was a potent agonist. ETYIKPWWVWL did not stimulate GTPgammaS binding but inhibited the stimulation by formyl-NleLeuPhe. It also blocked beta arrestin translocation and receptor downregulation induced by formyl-Nle-Leu-Phe. This indicates that formyl peptide receptor may be important in viral infections and that variations in its sequence among individuals may affect their likelihood of viral and bacterial infections.
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PMID:Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor. 1684 82

siVirus (http://siVirus.RNAi.jp/) is a web-based online software system that provides efficient short interfering RNA (siRNA) design for antiviral RNA interference (RNAi). siVirus searches for functional, off-target minimized siRNAs targeting highly conserved regions of divergent viral sequences. These siRNAs are expected to resist viral mutational escape, since their highly conserved targets likely contain structurally/functionally constrained elements. siVirus will be a useful tool for designing optimal siRNAs targeting highly divergent pathogens, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), influenza virus and SARS coronavirus, all of which pose enormous threats to global human health.
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PMID:siVirus: web-based antiviral siRNA design software for highly divergent viral sequences. 1684 46

International adoptions have become increasingly common in the United States. Children awaiting international adoption and families traveling to adopt these children can be exposed to a variety of infectious diseases. Compared with the United States, foreign countries often have different immunization practices and methods of diagnosing, treating, and monitoring disease. Reporting of medical conditions can also differ from that of the United States. The prevalence of infectious diseases varies from country to country and may or may not be common among adopted children. The transmission of tuberculosis, hepatitis B, and measles from adopted children to family members has been documented. Furthermore, infectious organisms (e.g., intestinal parasites), bacterial pathogens (e.g., Bordetella pertussis and Treponema pallidum), and viruses (e.g., human immunodeficiency virus and hepatitis viruses) may cause clinically significant morbidity and mortality among infected children. Diseases such as severe acute respiratory syndrome or avian influenza have not been reported among international adoptees, but transmission is possible if infection is present. Family members may be infected by others during travel or by their adopted child after returning home. Families preparing to adopt a child from abroad should pay special attention to the infectious diseases they may encounter and to the precautions they should take on returning home.
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PMID:International adoption: issues in infectious diseases. 1694 42


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