Selective Targeting of ApisOBP7 with Indole-2-Carboxylates as a Strategy for Developing Novel Aphid Repellents

Targeting odorant-binding proteins (OBPs) is a promising strategy for developing sustainable, behavior-modifying pest control agents. The unfamiliarly highly expressed OBP7 from Acyrthosiphon pisum (ApisOBP7) is a known binder of aphid alarm pheromone (E)-β-farnesene. Here, indole was identified as a moderate binder of ApisOBP7 (K_i = 28.47 μM) with repellent activity against A. pisum (repellent rate = 32.67%). Using this scaffold, 15 novel indole-2-carboxylate derivatives were designed and synthesized to discover selective ligands for ApisOBP7. Compound B02 exhibited an excellent affinity (K_i = 2.73 μM) to ApisOBP7. Molecular dynamics simulations suggested its high affinity originated from strong hydrophobic interactions and key hydrogen bonds. This strong binding conferred efficient repellency for B02 with 57.33% repellency rate at a 5 μg dose. Critically, RNAi study on ApisOBP7 significantly reduced repellent activity of indole (from 32.67% to 10%) and B02 (from 57.33% to 20%). This work validates ApisOBP7 as a valuable target for novel aphid repellent design.