Pharmacological targets and emerging treatments for respiratory syncytial virus bronchiolitis (original) (raw)
Related papers
Challenges and opportunities in developing respiratory syncytial virus therapeutics
The Journal of infectious diseases, 2015
Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial virus (RSV) infections. The practicalities of clinical trials and establishing reliable outcome measures in different target groups were discussed in the context of the regulatory pathways that could accelerate the translation of promising compounds into licensed agents. RSV drug development is hampered by the perceptions of a relatively small and fragmented market that may discourage major pharmaceutical company investment. Conversely, the public health need is far too large for RSV to be designated an orphan or neglected disease. Recent advances in understanding RSV epidemiology, improved point-of-care diagnostics, and identification of candidate antiviral drugs argue that the major obstac...
Pharmacologic Advances in the Treatment and Prevention of Respiratory Syncytial Virus
Clinical Infectious Diseases, 2010
Currently, only 2 drugs have been approved for the treatment of respiratory syncytial virus (RSV). Palivizumab is a monoclonal antibody for the prevention of RSV in high-risk children. Ribavirin is approved for treatment of severe RSV disease; however, its effectiveness in improving outcomes is questionable. During the past 40 years, many obstacles have delayed the development of safe and effective vaccines and treatment regimens. This article reviews these obstacles and presents the novel development strategies used to overcome many of them. Also discussed are promising new antiviral treatment candidates and their associated mechanism of action, the significant advances made in vaccine development, and exciting, new studies directed at improving outcomes through pharmacologic manipulation of the host response to RSV disease. Respiratory syncytial virus (RSV) is the leading cause of pediatric viral respiratory tract infections. The World Health Organization estimates an annual mortality rate of ∼160,000 deaths worldwide [1]; more inclusive all-cause mortality rates related to RSV approach 600,000 deaths [2]. RSV is also the second leading cause of viral death in elderly individuals [3]. By 18 months of age, 87% of children have developed RSVspecific antibodies [4]; by 3 years of age, virtually all children have been infected. In the United States alone, RSV infection results in 1120,000 childhood hospitalizations and up to 500 deaths [5]. Compared with influenza, RSV accounts for 19 times more deaths in children younger than 1 year [6-11]. Only 2 US Food and Drug Administration (FDA)-approved drugs are currently available for RSV disease. Palivizumab is indicated for RSV prevention in high-risk infants, including those with chronic lung disease, those with congenital heart disease, and those born prematurely [12]. This indication is based on hospitalization rates that are ∼5 times greater in highrisk versus non-high-risk infants. However, among all infants hospitalized with severe RSV disease, ∼70% are term infants
Expert Opinion on Pharmacotherapy, 2003
Respiratory syncytial virus (RSV) infection causes a huge burden to the health service, as it results in a large number of in-patient days each year and increases the risk of asthma in childhood. In the acute phase, therapy is supportive as bronchodilators and corticosteroids have resulted, at best, only in short-term benefits; promising treatments for ventilated patients, such as exogenous surfactant, require further testing. Passive immunoprophylaxis reduces hospital admission in high risk groups. In the prevention of chronic respiratory morbidity following RSV infection, however, studies are needed to determine whether immunoprophylaxis will have a useful role and to identify which drug treatment will be most cost-effective.
Pharmacotherapy of respiratory syncytial virus infection
Current Opinion in Pharmacology, 2010
Respiratory syncytial virus is the most common cause of severe lower respiratory disease in infants and young children. Its importance as a pathogen in the elderly and in the immunocompromised is becoming more clearly understood. RSV infection in infancy may lead to chronic lung disease ion later life. Newer forms of therapy are needed. This review will discuss the status of many types of compounds that interfere with RSV infection, including antibodies, inosine-5 0monophosphate dehydrogenase (IMPDH) inhibitors, fusion inhibitors, entry inhibitors, anti-sense RNA inhibitors, and nucleoprotein inhibitors.
Oral Efficacy of a Respiratory Syncytial Virus Inhibitor in Rodent Models of Infection
Antimicrobial Agents and Chemotherapy, 2004
Updated information and services can be found at: These include: REFERENCES http://aac.asm.org/content/48/7/2448#ref-list-1 at: This article cites 40 articles, 16 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on August 24, 2013 by guest http://aac.asm.org/
Respiratory syncytial virus: current and emerging treatment options
ClinicoEconomics and Outcomes Research, 2014
Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis ®) has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.
Post-Infection A77-1726 Blocks Pathophysiologic Sequelae of Respiratory Syncytial Virus Infection
American Journal of Respiratory Cell and Molecular Biology, 2007
Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common cause of lower respiratory tract disease in infants worldwide, treatment has progressed little in the past 30 years. The aim of our study was to determine whether post-infection administration of de novo pyrimidine synthesis inhibitors could prevent the reduction in alveolar fluid clearance (AFC) and hypoxemia that occurs at Day 2 after intranasal infection of BALB/c mice with RSV. BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice after instillation of 5% bovine serum albumin into the dependent lung. Post-infection systemic treatment with leflunomide has no effect on AFC. However, when added to the AFC instillate, leflunomide's active metabolite, A77-1726, blocks RSV-mediated inhibition of AFC at Day 2. This block is reversed by uridine (which allows pyrimidine synthesis via the scavenger pathway) and not recapitulated by genistein (which mimics the tyrosine kinase inhibitor effects of A77-1726), indicating that the effect is specific for the de novo pyrimidine synthesis pathway. More importantly, when administered intranasally at Day 1, A77-1726, but not its vehicle dimethyl sulfoxide, maintains its beneficial effect on AFC and lung water content until Day 2. Intranasal instillation of A77-1726 at Day 1 also reduces bronchoalveolar lavage nucleotide levels, lung inflammation, and hypoxemia at Day 2 without impairing viral replication at Day 2 or viral clearance at Day 8. Post-infection intranasal or aerosolized treatment with pyrimidine synthesis inhibitors may provide symptomatic relief from the pathophysiologic sequelae of impaired AFC in children with RSV bronchiolitis.