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The Anopheles gambiae Insecticidal Targets Made Bare by In-silica Analysis

Abstract

seveml wot·ks had attempted to use genomics to explain the mode of mosquito t·esistance and pt·edict dmg tat·get. The use of insecticides in val'ious ways has been the majm· malal'ia vectot· conti'Ol stmtegy being deployed lately, mostly pyt·ethi'Oid, the majm· t·ecommended compound class fot· IRS, ITNs and LLITNs. Resistance to dmgs and insecticides has continually obstmcted vectm·/malal'ia contt·ol stntegies. The advet·t effect is so enonnous in the Sub-Sahamn Afl'ican; its socioeconomic impact is unquantifiable in evet·y measm·e. Thus, the quick necessity fm· the development and elucidation of potent, cheap and efficient new potential insecticidal tat·gets, especially those in the class pyt·ethi'Oid fm· the malal'ia vectot·, A. gambiae. In this wm·k, an updated Anopheles gambiae biochemical metabolic netwm·k (AnoCyc vel'l.O), othet·wise known as pathway genome database (PGDB) was extmcted, the database was t·econstt·ucted by developing a computational gmph model in an appi'Oach that modeled the metabolic netwot·k of the m·ganism as a bipat·tite gmph, deployed the concept of choke point, load point and t·eaction without deviation to detet·mine the essential enzymatic t·eactions in the netwm·ks. Each potential dmg tat·get to theit· coiTesponding gene/pi'Otein and such encoding pi'Otein sequences wet·e extmcted. (PDB) was blasted fot· genes that have stmctm·e m· homologue of >= 30 sequence identity. Finally, we deployed Ovet·ton and Bation Scm·e (OB-Scm·e) and Pat·Ct·ys pt·ediction to mnk pi'Oteins by theit' likely success in ct·ystallization. 61 potential insecticidal candidate tat·gets was made bat·e, one clinically validated insecticidal tat·get and othet·s with biological evidence in the litemtnt·e. Seven of these tat·gets ideally stand out and have no homology with othet· vetiebmtes. These in depth dissection of the biochemical metabolic netwm·ks of the Anopheles effectively identified the ideal gene pi'Oducts and specifically extmct essential enzymes as new potential insecticidal tat·get against A. gambiae

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