2.14 | Known and potential drug targets
All compound-related proteins were searched against target proteins from
ChEMBL v26(Anna et al.) using BLASTP (E≤1×10−10). We
screened out all types of single proteins in the ChEMBL database for
blasting. Known drug target were identified from available publications
and by searching for ‘anthelmintics’ in the DrugBank(S et al., 2017)
database. For potential drug targets, we screen out all the single
protein targets as described(Coghlan, Mutowo, O’Boyle, Lomax, &
Berriman, 2018) and made adjustments to evaluate each gene. We set a
score of ‘0/1’ considering six main factors: 1.
Similarity with ChEMBL drug
targets and a highly conserved alignment (>80%); 2. Lack
of human homologues; 3. Related to lethal, L3 arrest, flaccid, molt
defect and sterile phenotypes. Lethal phenotypes were identified in
WormBase WS240; 4. Whether the protein was a predicted chokepoint
enzyme(Tyagi, Seshadri, Parkinson, & Mitreva, 2018); 5. The protein was
predicted as an excretory/secretory protein (EP); (6)
The protein had a structure in the
PDBe(Sameer et al., 2016). In order to make the screening most
efficient, we searched for commercially available compounds against the
target protein in ZINC15(Sterling & Irwin, 2015). Finally, we selected
compounds approved in phase III or above as suggested chemical
compounds.