2.11 | Known and potential drug targets
All compound-related proteins were searched against target proteins from
ChEMBL v26 (Anna et al., 2012) using BLASTP
(E≤1×10−10). We screened out all types of single
proteins in the ChEMBL database for blasting. Known drug targets were
identified from available publications and by searching for
‘anthelmintics’ in the DrugBank (Wishart, Feunang, An, Lo, & Wilson,
2017) database. For potential drug targets, we screened out all the
single protein targets as described (Avril 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. Whether the protein
was predicted as an excretory/secretory protein (EP); and 6.
Whether 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.