Pulmonary surfactant as a versatile biomaterial to fight COVID-19

Herman, Lore; Smedt, Stefaan C. De; Raemdonck, Koen

doi:10.1016/j.jconrel.2021.11.023

Cited by 23 publications

(10 citation statements)

References 255 publications

(310 reference statements)

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“…SP-A and SP-D, presenting in airways and the alveolar regions, were found to bind to the S protein, thus mitigating infection of the epithelial cells through viral neutralization, agglutination, and enhanced phagocytosis. , In addition, a recent clinical trial showed that the DPPC levels in the bronchoalveolar lavage fluids of COVID-19 patients were lower than those in healthy controls . All this evidence justified the hypothesis that exogenous surfactant therapy, in which clinical surfactant preparations extracted from animals’ lungs are delivered to patients’ lungs, may be used as a supportive therapy to treat patients with COVID-19 and COVID-19-associated ARDS. − There have been multiple ongoing clinical trials in the past two years . Although the verdict is still out, preliminary reports have demonstrated promise for the surfactant therapy in managing the progress of COVID-19. , …”

mentioning

confidence: 84%

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers

Sun

et al. 2022

J. Phys. Chem. Lett.

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Pulmonary surfactant has been attempted as a supportive therapy to treat COVID-19. Although it is mechanistically accepted that the fusion peptide in the S2 subunit of the S protein plays a predominant role in mediating viral fusion with the host cell membrane, it is still unknown how the S2 subunit interacts with the natural surfactant film. Using combined bio-physicochemical assays and atomic force microscopy imaging, it was found that the S2 subunit inhibited the biophysical properties of the surfactant and induced microdomain fusion in the surfactant monolayer. The surfactant inhibition has been attributed to membrane fluidization caused by insertion of the S2 subunit mediated by its fusion peptide. These findings may provide novel insight into the understanding of bio-physicochemical mechanisms responsible for surfactant interactions with SARS-CoV-2 and may have translational implications in the further development of surfactant replacement therapy for COVID-19 patients.

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mentioning

confidence: 84%

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers

Sun

et al. 2022

J. Phys. Chem. Lett.

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“…The lung is an attractive target organ for applying RNA therapeutics for the treatment of lung-related pathologies. Unfortunately, inhalation therapy of RNA entails specific challenges, and currently, no RNA-based product is clinically approved for administration via the inhalation route. − Here, our aim was to further investigate siRNA-loaded CAD-LNPs for local pulmonary delivery . As stable MC3-NT LNPs with a reduced cholesterol fraction could be formulated via microfluidic mixing, we next sought to evaluate their in vitro siRNA delivery efficiency in H1299-eGFP lung epithelial cells.…”

Section: In Vitro Transfection Efficiency Of Cholesterol-reduced Cad-...mentioning

confidence: 99%

Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery

Bogaert,

Debisschop,

Ehouarne

et al. 2024

Nano Lett.

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The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component of state-of-the-art LNPs via microfluidic mixing. Improved cytosolic delivery of both siRNA and mRNA was achieved by partly replacing the cholesterol fraction of LNPs with CADs. The LNPs could cross the mucus layer in a mucus-producing air−liquid interface model of human primary bronchial epithelial cells following nebulization. Moreover, CAD-LNPs demonstrated improved epithelial and endothelial targeting following intranasal administration in mice, without a marked pro-inflammatory signature. Importantly, quantification of the CAD-LNP molar composition, as demonstrated for nortriptyline, revealed a gradual leakage of the CAD from the formulation during LNP dialysis. Altogether, these data suggest that the addition of a CAD prior to the rapid mixing process might have an impact on the composition, structure, and performance of LNPs.

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“…Moreover, SP-D serum levels are higher in COVID-19 patients ( n = 88) as compared to healthy subjects ( n = 20) and are furtherly increased in those with poor prognosis ( n = 33) [ 139 ]. Finally, due to the key role of SPs in pathogenesis of severe COVID-19, use of systemic or inhaled exogenous SPs as therapeutic options to prevent the most severe COVID-19 form has been proposed and currently there are several promising data in vivo evaluating effectiveness of these compounds [ 140 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance

et al. 2023

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The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic or cause a disease (COVID-19) characterized by different levels of severity. The main cause of severe COVID-19 and death is represented by acute (or acute on chronic) respiratory failure and acute respiratory distress syndrome (ARDS), often requiring hospital admission and ventilator support.The molecular pathogenesis of COVID-19-related ARDS (by now termed c-ARDS) is still poorly understood. In this review we will discuss the genetic susceptibility to COVID-19, the pathogenesis and the local and systemic biomarkers correlated with c-ARDS and the therapeutic options that target the cell signalling pathways of c-ARDS.

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Pulmonary surfactant as a versatile biomaterial to fight COVID-19

Cited by 23 publications

References 255 publications

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers

Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery

Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance

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