Pulmonary surfactant lipids inhibit infections with the pandemic H1N1 influenza virus in several animal models

Abstract

The influenza A (H1N1)pdm09 outbreak in 2009 exemplified the problems accompanying the emergence of novel influenza A virus (IAV) strains and their unanticipated virulence in populations with no pre-existing immunity. Neuraminidase inhibitors (NAIs) are currently the drugs of choice for intervention against IAV outbreaks, but there are concerns that NAI-resistant viruses can transmit to high-risk populations. These issues highlight the need for new approaches that address the annual influenza burden. In this study, we examined whether palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI) effectively antagonize (H1N1)pdm09 infection. POPG and PI markedly suppressed cytopathic effects and attenuated viral gene expression in (H1N1)pdm09-infected Madin-Darby canine kidney cells. POPG and PI bound to (H1N1)pdm09 with high affinity and disrupted viral spread from infected to noninfected cells in tissue culture and also reduced (H1N1)pdm09 propagation by a factor of 102 after viral infection was established in vitro. In a mouse infection model of (H1N1)pdm09, POPG and PI significantly reduced lung inflammation and viral burden. Of note, when mice were challenged with a typically lethal dose of 1000 plaque-forming units of (H1N1)pdm09, survival after 10 days was 100% (14 of 14 mice) with the POPG treatment compared with 0% (0 of 14 mice) without this treatment. POPG also significantly reduced inflammatory infiltrates and the viral burden induced by (H1N1)pdm09 infection in a ferret model. These findings indicate that anionic phospholipids potently and efficiently disrupt influenza infections in animal models.

Airborne Transmission of COVID-19: Aerosol Dispersion, Lung Deposition, and Virus-Receptor Interactions

“… 135 A wealth of in vitro and in vivo studies have demonstrated that the biophysical function of PS can be inhibited by various particles, including nanoparticles, 144 − 148 nanoenabled sprays and drugs, 149 , 150 PM2.5, 151 − 153 and pathogens such as the H1N1 influenza virus. 154 Second, particles may interfere with PS metabolism and homeostasis in the alveolar hypophase. It was found that nanoparticles caused surfactant degradation from the more surface active large aggregates to less surface active small aggregates.…”

Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

“…It should also be noted that despite its ability to inhibit TLR activation and inflammation, PG in surfactant does not seem to be globally immunosuppressive. In fact, in animal models in vivo it protects against infection resulting from several viruses, including respiratory syncytial virus, influenza A (H3N2) and H1N1 [38] , [39] , [56] , by inhibiting the interaction of these viruses with their receptors on host cells ( Fig. 1 ).…”

Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID‐19): A State of the Art Review

“…However, intrinsic pulmonary surfactant has been found to be an important part of our innate immune system, and its use was recently shown to help prevent several respiratory viruses, such as H1N1 and influenza. [47][48][49] The pulmonary surfactant phospholipids are thought to prevent viral infections by inhibiting viral binding to epithelial cells. The use of surfactants to achieve the same results in the upper aerodigestive tract is intriguing but has not been studied.…”