Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses.
PMID: 24705721
2014
American journal of physiology. Lung cellular and molecular physiology
Abstract: Importantly, we now show that D325A
Abstract: The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V).
Abstract: We now show that replacement of D325 with serine to create D325S+R343V provided equal or increased neutralizing activity compared with D325A+R343V.
Abstract: We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV).
Molecular mechanisms of inhibition of influenza by surfactant protein D revealed by large-scale molecular dynamics simulation.
Result: We previously reported that D325A+R343V had equivalent neutralizing activity as native SP-D for a seasonal H3N2 strain .
Discussion: Based on experimental and computational evidence, we speculate that altered binding orientation and increased viral aggregation, perhaps coupled with the increased binding to HA
Discussion: Experimental evidence from that study shows that trimeric D325A+R343V NCRD is nearly as effective at aggregating IAV as is native dodecameric SP-D, whereas the WT NCRD trimer does not aggregate or neutralize the virus .
Discussion: From the interaction energies calculated from simulations WTS and DMS, D325A+R343V binds more strongly than WT to HA by approximately 19 kcal/mol.
IV mutation literature information.
PMID: 
2014
American journal of physiology. Lung cellular and molecular physiology
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