(389ao) Computational Modelling of Engineered Surfactant Protein D (SP-D) for Enhanced Trimannose Binding in Hemaglutinin of Influenza A Virus

Abstract: Surfactant Protein D (SP-D) is a hydrophilic surfactant component¹ and its bind with pathogen to uptake². It serves as an immune protein in the lungs, binding to surface glycans to prevent pathogen growth. A prior study reported that the Asp325Ala and Arg343Val mutations improved its binding to IAV hemagglutinin by optimizing the trimannose interaction and enhancing hydrogen bonding involving Glu333 ^3,4. This study focuses on engineering to create the most effective variant of SP-D to bind with trimannsoe of IAV. This current study focuses more on comparing different species of SP-D, including serum collectins, to find out the sequence differences and their stability. Additionally, how the different patterns of amino acid in different species help to bind with trimannose of IAV to inhibit IAV. In the prior study on different species, N303 in porcine, a highly sialylated N-linked glycan CRD provides interactions with the sialic acid-binding site of IAV⁵ and a tripeptide loop at the lectin binding site of porcine SP-D, located between residues Gly-326 and Gly-327, facilitates enhanced interactions with IAV⁶. Additionally, Bovidae serum collections enhance SP-D recognition of high mannose viral glycans and allow additional interactions with the Arg349 side chain⁷. Airborne pathogens often impact the respiratory system and contribute to various lung diseases. Based on the comparison of different species sequence, my focus is on re-engineering to produce a more effective variant of SP-D towards the trimannose on hemagglutinin (HA) of the Influenza A virus to inhibit IAV.

Reference:

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