Giving RSV some POP(G)

Abstract

A group at National Jewish Health has shown that a low-cost pulmonary surfactant called palmitoyl-oleoyl-phosphatidylglycerol, already known to attenuate respiratory syncytial virus-induced inflammatory responses, also inhibits binding of the virus to lung epithelial surfaces. 1 Although delivery and timing issues still need to be worked out, the surfactant's mechanism could offer a one-two punch to prevent or treat the infection.Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children younger than six months. Infection progresses from a mild upper airway condition that in most cases goes undiagnosed to a more serious and less accessible lower airway episode. Major risk factors leading to serious RSV infection, which in turn can cause acute respiratory distress syndrome (ARDS), are preterm birth, congenital heart defects and chronic lung disease.The one approved drug for RSV is Synagis palivizumab from AstraZeneca plc's MedImmune LLC business unit. The anti-RSV antibody is indicated to prevent RSV in high-risk children. The average wholesale price is about $1,000 per shot, which is given monthly through the RSV season. That price tag has limited its use to premature infants and precluded its application in full-term infants and young children. 2 Indeed, the American Academy of Pediatrics' Committee on Infectious Disease revised its treatment guidelines last year, based on "issues of efficacy, cost, and evidence-based medicine, " which could decrease the number of premature infants considered candidates for Synagis.The most notable changes included the recommendations for infants of 32-35 weeks gestational age. Those infants that are three months old or less at the start of RSV season who also have at least one more risk factor are recommended to receive the prophylactic. The 2006 recommendations suggested that the infants be six months or less. 3 The group at National Jewish Health has been looking for lowcost alternatives. Their strategy is to increase the levels of pulmonary surfactant, a lipoprotein mixture secreted by the lung that plays a role in host innate immunity. The surfactant they have their sights set on, palmitoyl-oleoyl-phosphatidylglycerol (POPG), can be obtained from suppliers for about $400 per gram.In September 2009, Dennis Voelker and colleagues at National Jewish Health reported that POPG decreased toll-like receptor 4 (TLR4) activation and inflammatory responses to lipopolysaccharide in the lungs of mice. 4 Now, his team has shown that POPG directly binds RSV in vitro and reduces viral infection and lung pathology in vivo. 1In RSV-infected epithelial cell lines, POPG liposomes prevented both viral spread to neighboring cells and cell death. When the cells were treated with the liposomes prior to infection, RSV was unable to bind to the cell surface and RSV-induced proinflammatory cytokine production was reduced compared with what was seen using control phospholipids.In mice, intranasal delivery of POPG liposomes plus RSV resulted in significantly lower viral infec...

Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids

“…Severe viral infections in humans by pH1N1 and SARS-CoV-2, can induce a cytokine storm including elevated levels of TNF-α, IL-6 and IL-8 [ 109 ]. These events contribute to the pathogenicity, the extensive pulmonary inflammation and the excessive lung damage [ 109 – 111 ]. Our preliminary data show the activities of POPG and PI as anti-viral and anti-inflammatory agents with significant potential for treating SARS-CoV-2 infections.…”

Eritoran insight for influenza treatment

“…Voelker is developing the antiviral and anti-inflammatory palmitoyloleoyl-phosphatidylglycerol (POPG) as a prophylactic and therapeutic for respiratory syncytial virus (RSV), influenza A virus, acute respiratory distress and acute lung injury. [5][6][7] "Importantly, the findings provide a new route for dealing with patient populations that fail to receive immunization or that respond poorly to immunization, " Voelker said. "The approach also provides a new avenue for treating emerging influenza A strains that are resistant to neuraminidase inhibitors, which currently constitute the primary therapeutics for patients without adequate immunity to the virus.…”