Searching for a scaffold for the in-silico design of an antibody for an epitope from Echinococcus granulosus histone H4.

MAGLIOCO ANDREA; AGÜERO FACUNDO ARIEL; PAULINO MARGOT; FUCHS ALICIA GRACIELA

Mar del Plata

Encuentro; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Fisiología

Cysticechinococcosis is a worldwide parasitic disease caused by Echinococcusgranulosus. The first line of diagnosis for cystic echinococcosis is constitutedby the image and the epidemiological status. Serology is the second line ofdiagnosis, based on the detection of antibodies, however it has false positivesand negatives due to the antigen used and conditions of the disease such as cystlocalization or age of the patient. Furthermore, antibodies can persist incirculation even in the absence of parasitic infection. The determination ofcirculating antigen would allow a more accurate diagnosis of the presence ofthe infection. We have recently identified that histone H4 (H4) from E.granulosus may be a relevant antigen for the detection of cysticechinococcosis. We obtained a validated structural model for H4 and predictedits linear (Lep) and conformational epitopes (Maglioco et al, 2022). The aim ofthis work was the selection of single-chain variable fragments (scFV) for thein-silico design of an antibody for H4 epitope. The structures scFv fromhumans, with heavy and light chains, available in PDB with a resolution of 1-2A (7VYT, 2YC1, 4UT7, 6J9O) were used. The CDRs were determined with Parapred.The docking of scFvCDRs with H4 (Lep 134-149, H4Lep) was obtained by ZDOCK. Thepart of H4 that did not correspond to H4Lep was blocked and the binding of theCDRs to H4Lep was carried out. The highest scoring pose of each combinationscFvCDR:H4Lep was analyzed in MOE 2019 software. Three hydrogen bonds wereobtained for 7VYTCDRs:H4Lep; 2 hydrogen bonds and 1 ionic bond were obtainedfor 2YC1CDRs:H4Lep; 2 hydrogen bonds and 1 ionic bond were obtained for 4UT7CDRs:H4Lepand no ionic or hydrogen bonds were found in 6J9OCDRs:H4Lep. The Arg140, Phe145and Asp148 from H4Lep were the amino acids most involved in the interactionsfound. We conclude that 7VYT, 2YC1 and 4UT7 could be good scaffolds to continuethe in-silico design of an antibody for H4Lep.