Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor

Abstract

Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD–ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.

Unraveling the enigma: The emerging significance of pulmonary surfactant proteins in predicting, diagnosing, and managing COVID‐19

“…This implies that these synthetic peptides may function as competitive inhibitors, potentially obstructing the virus from attaching to the ACE2 receptor, thus either preventing infection or mitigating its severity. 48 …”

Pulmonary Surfactant: A Mighty Thin Film

“…672,673 It is notable that the SP-B-C allele is associated with an increased incidence of RDS and an elevated severity of ARDS. 676−678 679 Patients bearing this pathogen demonstrate higher titers of anti-SP-B and anti-SP-C antibodies. Similar to SP-B, whereas SP-C has been mainly examined for its ability to aid formation of a surface film, recent studies by a number of investigators have demonstrated altered innate immunity in mice either lacking or with mutant forms of SP-C. For example, SFPC −/− mice show enhance susceptibility to a number of pathogens, including P. aeruginosa, and to respiratory syncytial virus.…”

“…Recent studies utilizing surface plasmon resonance indicate SP-B may interact directly with the angiotensin-converting enzyme 2 receptor, thereby providing steric hindrance toward infection by COVID-19 virus . Patients bearing this pathogen demonstrate higher titers of anti-SP-B and anti-SP-C antibodies.…”