Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: DrugBank:BIOD00097 (anti-RSV)
466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory syncytial virus is a leading cause of respiratory disease in infants, young children, immunocompromized patients, and the elderly. Previous work has shown that RNase L, an antiviral enzyme of the interferon system, can be recruited to cleave RSVgenomic RNA by attaching tetrameric 2' 5'-linked oligoadenylates (2 5A) to an antisense oligonucleotide complementary to repetitive intergenic sequences within the RSV genome (2 5A antisense). RBI034, a 2'-O-methyl RNA-modified analogue of the 2 5A anti-RSV compound, was found to have enhanced antiviral activity in cell culture studies while also cleaving RSV genomic RNA in an RNase L- and sequence-specific manner. RBI034s efficacy in suppressing RSV replication in cell culture is 50 to 100 times better than ribavirin, the only approved drug for RSV infection. Here we show that the activity of 2 SA antisense compound can be further enhanced by a combination treatment with interferon or ribavirin. The anti-RSV activity resulting from combination treatment is more potent than either treatment alone. We also demonstrate that RBI034 is effective against RSV in three different species: mice, cotton rats, and African green monkeys.
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PMID:Targeted therapy of respiratory syncytial virus by 2-5A antisense. 1624 78

Respiratory syncytial virus (RSV) is the leading viral pathogen responsible for bronchiolitis and pneumonia in infants and young children worldwide. We have previously shown in the mouse model that treatment with an anti-RSV neutralizing monoclonal antibody (MAb) against the F glycoprotein of RSV, palivizumab, decreased lung inflammation, airway obstruction, and postmethacholine airway hyperresponsiveness. MEDI-524, or Numax, is a new MAb derived from palivizumab with enhanced neutralizing activity against RSV. We compared the effects of these two MAbs on different markers of disease severity using the murine model of RSV infection. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or MEDI-524 was administered once at either 24 h before or 48 h after RSV inoculation. Regardless of the time of administration, all treated mice showed significantly decreased RSV loads in bronchoalveolar lavage samples measured by plaque assay. Only MEDI-524 given at -24 h significantly decreased lung RSV RNA loads on days 5 and 28 after RSV inoculation. Pulmonary histopathologic scores, airway obstruction, and postmethacholine airway hyperresponsiveness were significantly reduced in mice treated with MEDI-524 at 24 h before inoculation, compared with untreated controls and the other regimens evaluated. MEDI-524 was superior to palivizumab on several outcome variables of RSV disease assessed in the mouse model: viral replication, inflammatory and clinical markers of acute disease severity, and long-term pulmonary abnormalities.
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PMID:Comparative effects of two neutralizing anti-respiratory syncytial virus (RSV) monoclonal antibodies in the RSV murine model: time versus potency. 1625 14

Human respiratory syncytial virus (RSV) is the most common worldwide cause of lower respiratory tract infections (LRI) in infants less than 6 months of age. The prophylaxis against RSV infection by vaccination has been unsuccessful because of its adverse effects. As antiviral drug, ribavirin spray (aerosol) had been used clinically and reduces the amount of virus load, without reducing the necessity of symptomatic therapy and the duration of hospitalization. Therefore RSV LRI has been treated mainly symptomatically. Recently humanized anti-RSV F protein monoclonal antibody was developed and prescribed for prevention in high-risk infants such as premature ones and those with chronic lung and congenital heart diseases. It reduced the incidence of hospitalization significantly. It has been introduced in clinical use in Japan following to Western countries. On the other hand, a number of anti-RSV drugs have now been investigation; however, no valuable drugs for clinical use have been yet developed.
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PMID:[Respiratory syncytial virus]. 1630 33

Human respiratory syncytial virus (RSV) is the most common worldwide cause of lower respiratory tract infections (LRI) in infants less than 12 months of age. RSV isolates can be divided into group A and B. In addition, there were many genotypes within each group, and these genotypes have evolved global setting with temporal and geographic clustering. Many cellular genes encoding cytokines and chemokines which are activated by RSV infection has now been focused for the elucidation of pathophysiology of RSV LRI. The prophylaxis against RSV infection by vaccination has been unsuccessful because of its adverse effects. No valuable anti-RSV drugs for clinical use have been yet developed. Therefore RSV LRI has been treated mainly symptomatically. Recently humanized anti-RSV F protein monoclonal antibody was developed and prescribed for prevention in high-risk infants such as premature ones and those with chronic lung and congenital heart diseases. It reduced the incidence of hospitalization significantly.
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PMID:[Respiratory syncytial virus infection]. 1636 56

Respiratory syncytial virus (RSV) is a serious pathogen causing significant mortality and morbidity, especially in premature infants and infants with chronic lung disease or significant congenital heart disease. Therapy for RSV infection is essentially supportive, although several new compounds are under investigation. Therefore, immunoprophylaxis to prevent severe RSV disease in high-risk infants assumes great significance. Palivizumab, a humanized monoclonal antibody to RSV, significantly reduces hospitalization in the first 6 months in premature infants born at less than 35 weeks, infants less than 24 months of age with chronic lung disease and requiring treatment in the last 6 months, and in children 24 months or younger with hemodynamically significant heart disease. A new ultrapotent anti-RSV antibody (MEDI-524) appears to be more effective in animals than palivizumab and is undergoing clinical evaluation. There has been considerable progress in the development of vaccines; namely subunit, live attenuated, genetically recombinant virus and polypeptide vaccines. Plasmid DNA vaccines coding for parts of the F and G surface glycoproteins and vaccinia vector vaccines are also being evaluated. Maternal immunization has the potential to prevent RSV disease in early infancy. RSV prophylaxis has seen tremendous progress in the last decade.
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PMID:Prevention and treatment of respiratory syncytial virus infection in infants: an update. 1660 25

Infection of infants in their first year of life, children and elderly people with the respiratory syncytial virus (RSV) endangers the life of the patient. An attempt to develop a formalin-inactivated RSV (FI-RSV) vaccine during the 1960s resulted in an aggravated infection in immunized children, leading to hospitalization, while infection of non-immunized children produced much milder symptoms. The reason for this remained an enigma, one which was gradually solved over the last decade by many researchers who studied the molecular biology of RSV infection of respiratory ciliary cells. Clinical studies of RSV-infected patients indicated increased levels of Th2 cytokines and IgE in the patients' sera, suggesting that an allergy-like condition developed during infection. The biomarkers of allergy caused by endogenous or environmental allergens include a marked increase of the Th2 cytokine IL-4 and IgE non-neutralizing antibodies to the allergen. The way allergens trigger allergy was deciphered recently, and will be discussed later. Studies of RSV infection led to the suggestion that RSV patients suffer from allergy prior to RSV infection, a concept that was later abandoned. Studies on HIV-1 [Y. Becker, Virus Genes 28, 319-331 (2005)] research led me to the hypothesis that since HIV-1 infection induces a marked increase of IL-4 and IgE in serum, an allergy-like condition, the AIDS stage is the result of an allergen motif that is embedded in the shed viral gp120 molecules. It is hypothesized that the viral-soluble G glycoprotein (sG) contains a T cell superantigen (Tsag) that is capable of binding to the V(H)3 domain of IgE/FcepsilonRI(+) hematopoietic cells, basophils, mast cells and monocytes, similar to the case of allergens, and that this aggregation causes these innate system cells to degranulate and release large amounts of Th2 cytokines (IL-4, IL-5, IL-10, IL-13) into the blood. The way these Th2 cytokines skew the Th1/Th2 balance toward Th2 > Th1 will be discussed. The aim of the present review is to base RSV pathogenicity on the numerous very good analyses of the virus genes and to suggest a therapeutic approach to treatment that is directed at preventing the inhibitory effects of Th2 cytokines on the adaptive immune system of the patients, instead of inhibiting RSV replication by antivirals. The review of the molecular research on the role of the viral fusion (F) and attachment (G) glycoproteins of RSV provided information on their role in the virus infection: early in infection the F glycoprotein induces Th1 cells to release the Th1 cytokines IL-2, IL-12 and IFN-gamma to activate precursors CTLs (pCTLs) to become anti-RSV CTLs. The G and sG glycoproteins attach to FKNR1(+) ciliary respiratory epithelial cells as well as directly to eosinophils to the lungs. The sG T cell antigen can also induce the release of large amounts of Th2 cytokines from CD4(+) T cells and from FCepsilonRI(+) mast cells, basophils and monocytes. By comparison to HIV-1 gp120 it is possible to show that in the G and sG proteins the T cell antigen resembles the CD4(+) T cell superantigen (=allergen) domain of HIV-1 gp120 which aggregates with IgE/FCepsilonRI(+) hematopoietic cells. The increased IL-4 level in the serum inhibits the adaptive immune response: IL-4Ralpha(+) Th1 cells stop Th1 cytokine synthesis and IL-4Ralpha(+) B cells stop the synthesis of antiviral IgG and IgA and switch to IgE synthesis. In addition, the hematopoietic cells release histamine and prostaglandin which induce wheezing. The gradual increase of sG molecules creates a gradient of fractalkine (FKN) which directs IL-5-activated eosinophils to the lungs of the patient.
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PMID:Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy--a review. 1697 40

Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.
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PMID:Viral infection of the lungs through the eye. 1705 May 96

Human respiratory syncytial virus (RSV) is a major viral pathogen of the lower respiratory tract of infants and young children worldwide. No effective prevention measure is available. Attenuated Salmonella strains expressing heterologous antigens can be delivered by the oral route, triggering efficient antigen-specific humoral, cellular, and mucosal immunity. In this study, we orally administered attenuated Salmonella strain SL7207, carrying the plasmid pcDNA3.1/F expressing the RSV F gene, to BALB/c mice and showed significant elevations of serum anti-RSV IgG and bronchoalveolar lavage secretory IgA as compared with the control group carrying empty plasmid (p<0.001). The ratio of IgG1 and IgG2a was 0.96. The experimental group also showed a stronger cytotoxic T cell response (p<0.01 at effector:target ratios of 100:1 and 50:1) and a higher stimulation index value of T cell proliferation (p<0.05) than the respective control group. RSV titers in the lung homogenates of the experimental group on day 3 and day 5 postchallenge were lower than in the control group (p<0.05). Histopathological analysis showed obvious differences in infiltration of inflammatory cells and pulmonary alveolar wall thickness (p<0.01) between the two groups. In summary, our results demonstrate the potential of orally administered SL7207-based DNA vaccines against RSV infection.
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PMID:Oral respiratory syncytial virus (RSV) DNA vaccine expressing RSV F protein delivered by attenuated Salmonella typhimurium. 1769 64

Respiratory syncytial virus (RSV) infection is associated with secondary bacterial infections caused by nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae. The pathogenesis of these complications is not completely understood; however, viral infection of respiratory epithelial cells promotes colonization by these bacteria. In the present study, RSV virions associated with NTHi and pneumococci in an inoculum-dependent manner in a fluid-phase binding assay. Adherence of NTHi and S. pneumoniae to epithelial cells transiently expressing RSV G glycoprotein was 2- and 2.2-fold higher, respectively, than adhesion to cells transfected with the vector alone (P <0.01). Furthermore, 4.6- and 6.2-fold larger numbers of NTHi and pneumococci bound to cells expressing a membrane-bound full-length RSV G protein than to cells expressing a truncated non-membrane-bound protein (P <or=0.005). Pre-incubating cells expressing membrane-bound G protein with blocking anti-RSV G antibodies reduced bacterial adherence by 78-84 % (P <or=0.005). These studies demonstrate that RSV G protein is a receptor for both NTHi and S. pneumoniae. Strategies to prevent this interaction may reduce the incidence of secondary bacterial complications of RSV infection.
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PMID:Nontypeable Haemophilus influenzae and Streptococcus pneumoniae bind respiratory syncytial virus glycoprotein. 1776 73

Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children. We followed 217 children from birth to 1 year of age. Nasal swabs and symptom diaries were collected monthly. Anti-hMPV and anti-RSV IgG antibodies by age 1 year were detected by ELISA, and nasal swabs were analysed for hMPV and RSV by RT-PCR. Logistic regression was used for risk factor analysis. Anti-hMPV IgG was found in 38 children (17.5%), and anti-RSV IgG in 172 children (79%). Risk factors for being anti-hMPV IgG-positive were: (1) being born in the spring (OR = 2.36; 95% CI:1.06-5.27), and (2) having older siblings (OR = 3.82; 95% CI:1.75-8.34). Risk factors for being anti-RSV IgG-positive were: (1) gestational age <38 weeks (OR = 3.39; 95% CI:1.42-8.05), (2) increasing paternal age (OR = 1.85 per 5 yrs; 95% CI:1.28-2.68), and (3) wall-to-wall carpeting (OR = 3.15; 95% CI:1.29-7.68). Being born in the spring was associated with decreased odds of being anti-RSV IgG-positive (OR = 0.27, 95% CI:0.09-0.85). Risk factors for RSV hospitalisation (n = 11) were: (1) older siblings (OR = 4.49; 95% CI: 1.08-18.73) and (2) smoking in the household (OR = 5.06; 95% CI: 1.36-18.76). Exclusive breastfeeding for the first 14 days of life protected against hospitalisation (OR = 0.21; 95% CI:0.06-0.79). In conclusion, this study identifies risk factors for mild and asymptomatic hMPV infections in infancy.
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PMID:A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life. 1817 83


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