Role of surfactant protein d (sp-d) in COVID-19

ABSTRACT

Rationale Surfactant protein D (SP-D) is a major immune protective molecule produced in the respiratory epithelium. SP-D binds to specific pathogen surfaces through its carbohydrate recognition (lectin) domain, that helps in their neutralization and clearance by phagocytes. SP-D also acts as an anti-inflammatory molecule. We hypothesized that SP-D plays a protective role in COVID-19. Methods: Polar+, a novel quantum computing algorithm for molecular pruning, and classical in silico modeling were used to investigate potential binding sites between SP-D and SARS CoV2. Electronegativity and topologically oriented molecular pruning, calculation of electronic force-fields and electrostatic binding combined with protein-protein docking, geometric fitting and assessment of protein glycosylation sites were employed. SP-D-/- mouse lung was used to study expression of the SARS-CoV-2 viral entry molecules TMPRSS2 and ACE2. Plasma from COVID-19 patients was studied for SP-D leakage, cytokine levels and lipid mediators. Results: We found that SP-D potentially binds to the same SARS CoV-2 glycoprotein (S protein) that it utilizes to bind the cellular receptor, ACE2, with high affinity. However, SP-D binds to subunit 2, instead of subunit 1 (that ACE2 utilizes). Additional studies will need to determine if SP-D binding affects S protein and ACE2 interactions. We also found that SP-D-/- mice had increased expression of the TMRSS2 gene in the lung and that both TMPRSS2 and ACE2 mRNA levels were increased during lung injury, amplified by the lack of SP-D. SP-D leakage from the lung to the circulation was significantly increased in COVID- 19 patients and correlated with expression of pro-neutrophilic inflammatory markers. Conclusions: We speculate that SP-D aids in the protection from SARS CoV2 infection by both acting as a potential natural decoy to prevent coronavirus entry into airway epithelial cells and by attenuating the expression of the viral entry receptor TMPRSS2. Oxidative lung injury results in SP-D leak into the circulation denoting disease severity in COVID-19 patients. (AH) .