SEARCHING FOR A SCAFFOLD FOR THE IN-SILICO DESIGN OF AN ANTIBODY FOR AN EPITOPE FROM ECHINOCOCCUS GRANULOSUS HISTONE H4

MAGLIOCO A; AGUERO F; PAULINO M; FUCHS A

Mar del plata

Congreso; Reunión anual de Sociedades de Biociencias; 2022

Cystic echinococcosis (CE) is a worldwide parasitic disease causedby E. granulosus. The first line of diagnosis is based on cyst imagingand the epidemiological status. Serology is based on the detectionof antibodies (Ab); however, it has false positives and negatives dueto the antigen (Ag) used and the cyst localization and stage. Furthermore, Ab can persist in circulation even in the absence of theinfection. The determination of circulating Ag would allow a moreaccurate diagnosis of the presence of the infection. We have recently identified that histone H4 (H4) from E. granulosus could be arelevant Ag for the detection of CE. We obtained a validated modelfor H4 and predicted its linear (Lep) and conformational epitopes(Maglioco et al, 2022). The aim of this work was the selection ofsingle-chain fragment variable (scFv) for the in-silico design of anantibody for H4 epitope. The scFv from humans, with heavy (VH)and light chains (VL), available in PDB with a resolution of 1-2 Å(7VYT, 2YC1, 4UT7, 6J9O) were used. The CDRs were determinedwith Parapred. The docking of scFvCDRs with H4 (Lep 134-149, H4Lep) was obtained by ZDOCK. The part of H4 that did not correspond to H4Lep was blocked and the binding of the CDRs to H4Lepwas carried out. The highest scoring pose of each scFvCDRs:H4Lep was analyzed in MOE 2019 software. Three hydrogen bonds(VL-Ser31:H4-Phe145, VL-Gly50:H4-Asp148 and VH-Ser56:H4-Arg136) were obtained for 7VYT; 2 hydrogen bonds (VL-Ser163:H4-Arg140 and VH-Val101:H4-Phe145) and an ionic interaction (VLAsp182:H4-Arg140) were obtained for 2YC1; 2 hydrogen bonds(VH-Tyr100A:H4-Arg144 and VH-Tyr100F:H4-Ser138) and an ionicinteraction (VL-Lys53:H4-Asp148) were obtained for 4UT7 and nointeraction was found for 6J9O. We concluded that 7VYT, 2YC1, and4UT7 could be good scaffolds to continue the in-silico design of anAb for H4Lep. Further experiments will be required to analyze therelevance of the described interactions for H4 recognition.