Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that toll-like receptor 4 (TLR4) was activated after RSV infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced autophagy and apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor.

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ReFRAME drug-repurposing library consisting of 12,000 small molecules against RSV. We identify 21 primary candidates including RSV F and N protein inhibitors, five HSP90 and four IMPDH inhibitors. We select lonafarnib, a licensed farnesyltransferase inhibitor, and phase III candidate for hepatitis delta virus (HDV) therapy, for further follow-up. Dose-response analyses and plaque assays confirm the antiviral activity (IC50: 10-118 nM). Passaging of RSV with lonafarnib selects for phenotypic resistance and fixation of mutations in the RSV fusion protein (T335I and T400A). Lentiviral pseudotypes programmed with variant RSV fusion proteins confirm that lonafarnib inhibits RSV cell entry and that these mutations confer lonafarnib resistance. Surface plasmon resonance reveals RSV fusion protein binding of lonafarnib and co-crystallography identifies the lonafarnib binding site within RSV F. Oral administration of lonafarnib dose-dependently reduces RSV virus load in a murine infection model using female mice. Collectively, this work provides an overview of RSV drug repurposing candidates and establishes lonafarnib as a bona fide fusion protein inhibitor.

Luteolin-7-O-glucoside promotes macrophage release of IFN-ß by maintaining mitochondrial function and corrects the disorder of glucose metabolism during RSV infection.

Respiratory syncytial virus (RSV) pneumonia is the main cause of acute bronchiolitis in infants. Luteolin-7-O-glucoside (LUT-7G) is a natural flavonoid, which exists in a variety of plants and has the potential to treat viral pneumonia. We established RSV pneumonia mouse models and RSV-infected cell models. Clodronate liposomes were used to deplete macrophages. We used HE staining and immunohistochemistry to determine inflammatory damage and virus replication. We detected the expression levels of inflammatory factors and IFN-ß through qPCR and ELISA. JC-1 kit was used for detecting the cell mitochondrial Membrane potential (MMP). ROS, SOD, and MDA kits were used for detecting intracellular oxidative stress damage. Metabolites of TCA in lung tissue and serum of mice were detected by GC-MS. Pharmacodynamic studies have shown that intervention with LUT-7G can alleviate lung tissue damage caused by RSV infection, inhibit RSV replication, and downregulate TNF-α, IL-1ß, and IL-6 mRNA expression. LUT-7G upregulated the IFN-ß content and the expression of IFN-ß, ISG15, and OAS1 mRNA. In vitro, LUT-7G inhibited RSV-induced cell death, reversed the RSV-induced decrease of MMP and decreased intracellular oxidative stress. Target metabonomics showed that RSV infection upregulated the levels of glycolysis and TCA metabolites in lung tissue and serum, while LUT-7G could improve the disorder of glucose metabolism. The results indicate that LUT-7G can promote the release of IFN-ß in the lung, alleviate inflammatory damage, and inhibit RSV replication during RSV infection. These effects may be achieved by protecting the mitochondrial function of alveolar macrophages and correcting the disorder of glucose metabolism.

Palivizumab prophylaxis in preterm infants and subsequent wheezing/asthma: 10-year follow-up study.

BACKGROUND: Respiratory syncytial virus (RSV) causes not only infantile recurrent wheezing but also the development of asthma. To investigate whether palivizumab, an anti-RSV monoclonal antibody, prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing and/or development of asthma, at 10 years of age. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 6 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice (SCELIA study). Here, we followed these subjects until 10 years of age. Parents of study subjects reported the patients' physician's assessment of recurrent wheezing/asthma, using a report card and a novel mobile phone-based reporting system using the internet. The relationship between RSV infection and asthma development, as well as the relationship between other factors and asthma development, were investigated. RESULTS: Of 154 preterm infants enrolled, 113 received palivizumab during the first year of life. At 10 years, although both recurrent wheezing and development of asthma were not significantly different between the treated and untreated groups, maternal smoking with aeroallergen sensitization of the patients was significantly correlated with physician-diagnosed asthma. CONCLUSIONS: In contrast to the prior study results at 6 years, by 10 years palivizumab prophylaxis had no impact on recurrent wheezing or asthma, but there was a significant correlation between maternal passive smoking with aeroallergen sensitization and development of asthma by 10 years of age.

In-vivo and human evidence for potential efficacy of therapeutic polyclonal RSV neutralizing antibodies for palivizumab-resistant RSV infections.

BACKGROUND: Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®, RI-001, RI-002) are used with ribavirin in RSV-infected immunocompromised patients, with debated efficacy. Palivizumab-resistance (PR) can arise during treatment of persistent infections in this population. RSV-IG may confer benefit in PR-RSV infection. METHODS: RSV-IG [RI-001] was provided for an immunocompromised infant with RSV-pneumonitis refractory to ribavirin and palivizumab. RSV-neutralizing antibody, respiratory RSV load (qPCR), and F-gene-sequence-detection of PR was determined. Prophylactic RSV-IG [RI-002] or palivizumab was administered in a cotton-rat model infected with wild-type and PR-RSV. Lung RSV load and neutralizing antibody were measured. RESULTS: As protective RI-001-neutralizing antibody titers waned in the infant, a subpopulation of PR-escape mutants were detected with a fatal RSV-burden in the lungs. In PR-RSV-infected cotton rats, prophylactic RI-002 reduced RSV-load in the lungs (2.45 vs 0.28 log10 PFU/g lung-tissue reduction, respectively, p < 0.05) and provided protective RSV-neutralizing antibody. CONCLUSIONS: RSV-IG and ribavirin use in immunocompromised patients requires further study.

Licochalcone A plays dual antiviral roles by inhibiting RSV and protecting against host damage.

Respiratory syncytial virus (RSV) causes lower respiratory tract diseases and bronchiolitis in children and elderly individuals. There are no effective drugs currently available to treat RSV infection. In this study, we report that Licochalcone A (LCA) can inhibit RSV replication and mitigate RSV-induced cell damage in vitro, and that LCA exerts a protective effect by reducing the viral titer and inflammation in the lungs of infected mice in vivo. We suggest that the mechanism of action occurs through pathways of antioxidant stress and inflammation. Further mechanistic results demonstrate that LCA can induce nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus, activate heme oxygenase 1 (HO-1), and inhibit reactive oxygen species-induced oxidative stress. LCA also works to reverse the decrease in I-kappa-B-alpha (IкBα) levels caused by RSV, which in turn inhibits inflammation through the associated nuclear factor kappa B and tumor necrosis factor-α signaling pathways. The combined action of the two cross-talking pathways protects hosts from RSV-induced damage. To conclude, our study is the first of its kind to establish evidence of LCA as a viable treatment for RSV infection.

Tryptophan-like side chain holding aptamers inhibit respiratory syncytial virus infection of lung epithelial cells.

Respiratory syncytial virus (RSV) is a leading cause of serious and even fatal acute lower respiratory tract infections in infants and in the elderly. Potent RSV neutralization has been achieved by antibodies that selectively bind the prefusion form of the viral fusion (F) protein. We hypothesised that similar potent neutralization could be achieved using F protein targeting aptamers. Aptamers have yet to reach their translational potential for therapeutics or diagnostics due to their short half-life and limited range of target-aptamer interactions; these shortcomings can, however, be ameliorated by application of amino acid-like side chain holding nucleotides. In this study, a stabilized version of the prefusion RSV F protein was targeted by aptamer selection using an oligonucleotide library holding a tryptophan-like side chain. This process resulted in aptamers that bound the F protein with high affinity and differentiated between its pre- and postfusion conformation. Identified aptamers inhibited viral infection of lung epithelial cells. Moreover, introduction of modified nucleotides extended aptamer half-lives. Our results suggest that targeting aptamers to the surface of viruses could yield effective drug candidates, which could keep pace with the continuously evolving pathogens.

T cell immune profiling of respiratory syncytial virus for the development of a targeted immunotherapy.

Respiratory syncytial virus (RSV)-associated viral infections are a major public health problem affecting the immunologically naïve/compromised populations. Given the RSV-associated morbidity and the limited treatment options, we sought to characterize the cellular immune response to RSV to develop a targeted T cell therapy for off-the-shelf administration to immunocompromised individuals. Here we report on the immunological profiling, as well as manufacturing, characterization and antiviral properties of these RSV-targeted T cells. A randomized, phase 1/2 clinical trial evaluating their safety and activity in haematopoietic stem cell transplant recipients as an off-the-shelf multi-respiratory virus-directed product is currently underway (NCT04933968, https://clinicaltrials.gov).

Ribavirin treatment for respiratory syncytial virus infection in patients with haematologic malignancy and haematopoietic stem cell transplant recipients: a systematic review and meta-analysis.

BACKGROUND: Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial. OBJECTIVES: To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection. DATA SOURCES: MEDLINE, Embase, and the Institute for Scientific Information Web of Science. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection. PARTICIPANTS: Patients with HM/HSCT. INTERVENTIONS: Ribavirin versus no ribavirin. ASSESSMENT OF RISK OF BIAS: The risk of bias in non-randomized studies of exposure (ROBIN-E). METHODS OF DATA SYNTHESIS: The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence. RESULTS: One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I2 = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I2 = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I2 = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I2 = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I2 = 71% (low certainty of evidence). CONCLUSIONS: Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents.

The effects of N-acetylcysteine on lung alveolar epithelial cells infected with respiratory syncytial virus.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the most common causes of acute lower respiratory infection in infants and young children. Mucolytic agents, such as acetylcysteine and carbocysteine have reported benefits in alleviating acute upper or lower respiratory infections. Among these, N-acetylcysteine (NAC) has cyto-protective effects when cells are infected with the RSV. MATERIALS AND METHODS: Our study investigated primarily the dose-dependent effects of NAC on respiratory alveolar epithelial (A549) cells when co-cultured with RSV in vitro. Three different concentrations of NAC were used, 0.1 mM, 1 mM, and 10 mM. The cytotoxicity of RSV-infected cells was measured by lactate dehydrogenase and antiviral activity of NAC on cell cultures was evaluated by immunofluorescence. RESULTS: Pre-treatment with the highest dose, 10 mM NAC, resulted in features of cell injury even without RSV infection. The proportion of cells infected by RSV and RSV-induced cell death decreased by more than 3-fold when cells were pre-treated with 1 mM NAC. Pre-treatment at the lowest dose, 0.1 mM, did not show any significant changes. CONCLUSION: A moderate dose of NAC (1 mM) appeared protective of RSV infection to lung alveolar epithelial cells. However, a higher dose of NAC (10 mM) may be relatively toxic and injurious to these cells.

New Inhibitors of Respiratory Syncytial Virus (RSV) Replication Based on Monoterpene-Substituted Arylcoumarins.

Respiratory syncytial virus (RSV) causes annual epidemics of respiratory infection. Usually harmless to adults, the RSV infection can be dangerous to children under 3 years of age and elderly people over 65 years of age, often causing serious problems, even death. At present, there are no vaccines and specific chemotherapeutic agents for the treatment of this disease, so the search for low-molecular weight compounds to combat RSV is a challenge. In this work, we have shown, for the first time, that monoterpene-substituted arylcoumarins are efficient RSV replication inhibitors at low micromolar concentrations. The most active compound has a selectivity index of about 200 and acts most effectively at the early stages of infection. The F protein of RSV is a potential target for these compounds, which is also confirmed by molecular docking and molecular dynamics simulation data.

Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of mortality and morbidity in children under the age of five. Despite this, there is still a lack of safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear. METHODS AND RESULTS: In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effects of andrographolide on RSV were analyzed via RSV N gene load and proinflammatory cytokine levels. The RNA transcriptome was sequenced, and data were analyzed by R software. Andrographolide-related target genes were extracted via network pharmacology using online databases. Lentiviral transfection was applied to knockdown the heme oxygenase-1 gene (Hmox1, HO-1). Results showed that andrographolide suppressed RSV replication and attenuated subsequent inflammation. Network pharmacology and RNA sequencing analysis indicated that the hub gene HO-1 may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, andrographolide exerted antiviral effects against RSV partially by inducing HO-1 but did not activate the antiviral interferon response. CONCLUSION: Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 expression in human airway epithelial cells, providing novel insights into potential therapeutic targets and drug repurposing in RSV infection.

Variation in clinical practice guidelines for use of palivizumab in preventing severe respiratory syncytial viral (RSV) disease in high-risk infants.

BACKGROUND: Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe respiratory syncytial viral infection in Australian high-risk infants remain unclear. METHODS: An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines. RESULTS: A total of 65 of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). According to the survey, infants most likely to be recommended palivizumab included preterm infants born <29 weeks gestational age (GA) (30%), children with chronic lung diseases (CLDs) born <32 weeks GA (40%), and with hemodynamically significant heart disease (35%). Many of the respondents (53%) stated that CPGs for palivizumab were developed locally. Literature search identified 20 guidelines (10 international and 10 domestic); 16 (80%) recommended palivizumab use in preterm infants, 16 (80%) recommended use in infants with CLD, 17 (85%) in congenital heart disease and 6 (30%) in bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low- or middle-income countries. CONCLUSIONS: Standardization of CPGs may improve clinical decision making around use of palivizumab in high-risk infants.

N-Acetyl-L-Cysteine Protects Airway Epithelial Cells during Respiratory Syncytial Virus Infection against Mucin Synthesis, Oxidative Stress, and Inflammatory Response and Inhibits HSPA6 Expression.

Objective. Respiratory syncytial virus (RSV) infection is an important cause of hospitalization of children worldwide, leading to significant morbidity and mortality. RSV infection leads to increasing inflammatory and apoptosis events in the airway epithelium through mechanisms involving ROS generation. The antioxidant N-acetyl-L-cysteine (NAC) has been shown to inhibit influenza virus replication and to reduce the secretion of inflammatory and apoptotic mediators during virus infection. The study aims to investigate the effects of NAC on human bronchial epithelial cells BEAS-2B and HSPA6 expression during RSV infection. Methods. CCK-8 assays were performed to evaluate cell survival. The production of proinflammatory factors, TNF-α, IL-6, IL-1ß, IL-18, and MUC5AC was examined by quantitative real-time PCR and ELISA. Oxidative stress was determined by reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)/glutathione disulfide (GSSG) ratio. Immunoblotting analysis of epidermal growth factor receptor (EGFR) and its phosphorylation was performed. The antiviral effect of NAC was assessed by determining viral titers using plaque assay. Results. RSV infection reduced cell survival, promoted the release of proinflammatory factors, increased the ROS production and MDA concentration, and diminished the SOD activity and GSH/GSSG ratio, all which were attenuated by NAC treatment. Accordingly, NAC treatment inhibited the activation of EGFR and MUC5AC in BEAS-2B cells with RSV infection. Furthermore, NAC administration resulted in a marked decrease in RSV-induced HSPA6 expression in BEAS-2B cells. Concomitantly, EPB treatment led to an evident inhibition of RSV fusion gene and viral replication in RSV-infected BEAS-2B cells. Conclusion. This work supports the use of NAC to exert antimucin synthesis, anti-inflammatory, antioxidant, and antiviral effects on airway epithelium during RSV infection.

Impact of immunoprophylaxis with palivizumab on respiratory syncytial virus infection in preterm infants less than 35 weeks in Colombian hospitals.

OBJECTIVE: To evaluate the impact of immunoprophylaxis with palivizumab in preterm infants less than 35 weeks in terms of hospitalization rate, intensive care unit requirement, and mortality. METHODS: A prospective cohort study was conducted at six Colombian hospitals. Preterm infants less than 35 weeks who received at least one dose of palivizumab during the first 6 months of life were included. The primary outcome was the hospitalization rate related to respiratory syncytial virus (RSV) infection. RESULTS: A total of 222 newborns participated in the study; 204 (91.8%) completed the 6-month follow-up, and three died during the study. 88.7% received a second dose of palivizumab, 79.7% a third, 34.7% a fourth, and 25.2% a fifth. The nonadjusted incidence rate of RSV infection was 2.4%, and the overall RSV-positive hospitalization rate was 1.9%. The proportion of patients that required Neonatal Intensive Care Unit (NICU) and mechanical ventilation in relation to RSV infection was 1.4%. Discharge with home oxygen, pulmonary dysplasia, and being younger than 6 months were significantly associated with respiratory infection. Furthermore, exposition to cigarette smoke was the only factor associated with increased risk of hospitalization. The group that required hospitalization received fewer doses of palivizumab (p = 0.049). No discontinuation of treatment due to adverse events were reported. No death was judged to be related to palivizumab. CONCLUSION: The hospitalization rate and the need for NICU admission were lower than those reported in the literature. In this real-life setting, palivizumab appears to be effective in preventing serious cases of RSV infection.

Ribavirin for Treatment of Subjects with Respiratory Syncytial Virus-Related Infection: A Systematic Review and Meta-Analysis.

INTRODUCTION: Respiratory syncytial virus (RSV)-associated diseases have caused an estimated 1.8 million hospital admissions and 40,000 deaths among children. RSV can cause lower respiratory tract infections (LRTIs) in all age groups, adults with comorbidities, and immunocompromised patients. The aim was to summarize the evidence concerning efficacy and safety of ribavirin in subjects diagnosed with RSV associated with LRTI. METHODS: A systematic review and meta-analysis were performed. Eligible studies were observational (> 10 subjects) and randomized-controlled trials of subjects with aerosol/oral ribavirin for RSV-LRTI. Comparator was supportive care or placebo. Systematic search on PubMed, Cochrane Library, and Web of Science databases was conducted between January 2001 and January 2022. PROSPERO register number: CRD42022308147. RESULTS: After retrieving 907 studies, 10 observational studies and 1 randomized controlled trial were included (4/11 high quality of evidence). Seven studies included subjects with haematological malignancy/stem cell transplant, two lung transplants, and two healthy individuals. A total of 788 subjects diagnosed with RSV infection were included; 14.3% of them presented with only LRTI. Among 445 subjects treated with ribavirin, 195 (43.8%) received an aerosolized formulation. Pooled meta-analysis showed no differences in mortality [risk ratio (RR): 0.63; 95% confidence interval (CI): 0.28-1.42] in all subjects treated with aerosol/oral ribavirin compared to supportive care. In subgroup analysis, mortality was significantly lower in haematological subjects (RR: 0.32; 95% CI: 0.14-0.71), but did not differ significantly in lung transplant recipients (RR: 0.89; 95% CI 0.31-2.56). Oral ribavirin (vs. supportive care) was associated with increased viral clearance (RR: 2.60; 95% CI: 1.35-4.99). Seventeen adverse events were reported among 119 subjects, but none were severe. CONCLUSION: Ribavirin should be considered for treatment of RSV-LRTI in haematological subjects. There is a lack of evidence to support its use in lung transplant recipients. Oral formulation appears to be an easier, safe, and cost-effective alternative to aerosolized ribavirin. Further advances needs to focus on newer antivirals.

Protein and Peptide Substances in the Treatment of Respiratory Syncytial Infection: Current State.

Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs.

A Systematic Review of European Clinical Practice Guidelines for Respiratory Syncytial Virus Prophylaxis.

BACKGROUND: Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe. METHODS: We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting. RESULTS: A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency. CONCLUSIONS: We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.

Ephedrae Herba and Cinnamomi Cortex interactions with G glycoprotein inhibit respiratory syncytial virus infectivity.

Although respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children, no effective therapies are available. Recently, RSV G, the attachment glycoprotein, has become a major focus in the development of therapeutic strategies against RSV infection. Treatment of RSV-infected cultured cells with maoto, a traditional herbal medicine for acute febrile diseases, significantly reduced the viral RNA and titers. RSV attachment to the cell surface was inhibited both in the presence of maoto and when RSV particles were pre-treated with maoto. We demonstrated that maoto components, Ephedrae Herba (EH) and Cinnamomi Cortex (CC), specifically interacted with the central conserved domain (CCD) of G protein, and also found that this interaction blocked viral attachment to the cellular receptor CX3CR1. Genetic mutation of CX3C motif on the CCD, the epitope for CX3CR1, decreased the binding capacity to EH and CC, suggesting that CX3C motif was the target for EH and CC. Finally, oral administration of maoto for five days to RSV-infected mice significantly reduced the lung viral titers. These experiments clearly showed the anti-RSV activity of EH and CC mixed in maoto. Taken together, this study provides insights for the rational design of therapies against RSV infection.