The interaction and mechanism of monoterpenes with tyramine receptor (SoTyrR) of rice weevil (Sitophilus oryzae)

Abstract

Rice weevils (Sitophilus oryzae) are pests that feed on grain products. One strategy employed in the safe pest management is the use of essential oils from plant materials as biopesticide. Monoterpene compounds, present in essential oils, are generally less acutely toxic than other conventional insecticides and are known to possess biopesticide activity against octopaminergic receptors (OAR). Tyramine receptor (TyrR) is a desired biopesticide target due to its absence in vertebrates and its role in insect's physiological and cellular response. In this study, the biochemical basis of monoterpenes and SoTyrR interactions were determined using in silico methods: ensemble docking, 3DQSAR analysis, and toxicity prediction. Ensemble docking results showed that the lead compounds has binding affinity of − 4.2 to − 6.8 kcal/mol. Four monoterpene compounds: terpinolene, carvacrol, carene, and pulegone were considered top hits based on their favorable binding affinity. Furthermore, hydrophobic interactions of monoterpenes with residues Asp114, Val404, Lys189, Leu190, Tyr196, Phe397, and Tyr401 stabilized the observed docking poses. Upon consolidation of docking and 3DQSAR results, we functionalized top hit ligands and showed significant increase in the average binding affinity of candidate compounds, ranging from − 4.7 to − 8.3 kcal/mol. A carene derivative exhibited the highest binding energy of − 8.3 kcal/ mol with a calculated K i of 0.547 μM which surpassed the known activators of OAR. The top hit modified ligands were also clear of toxicity risks as predicted by Osiris Property Explorer. This work could provide insights in the development of effective biopesticides for rice weevils that is less toxic than conventional pesticides.

The Insect Type 1 Tyramine Receptors: From Structure to Behavior

“…This allosteric modulation of TAR1 was shown to interfere with the receptor expression and subsequently with the insect physiology and behavior [ 61 ]. Recent data have revealed that in silico prediction of the structural interaction between monoterpenes and S. oryzae TAR1 might provide new insights and possibly new molecules for TAR1-related pest control [ 95 ].…”

Specificity of Monoterpene Interactions with Insect Octopamine and Tyramine Receptors: Insights from in Silico Sequence and Structure Comparison

“…Carene, pulegone, carvacrol, terpinolene, and thymol are determined to be top hits to more than one OAR/TAR. Four of these monoterpenes are also classified as top hits in the ensemble docking of SoTyrR in a separate study . On the other hand, top hits sabinene and camphene are unique to HvOctR; (+)-3-bromocamphor is unique to PxTyrR; and B-camphol is unique to SoTyrR.…”

“…Essential oil constituents such as monoterpenes have been shown to target arthropod proteins such as acetylcholinesterase (ACHE) and octopaminergic and tyraminergic receptors to induce neuromodulatory and neurotoxicity effects. − Among plant secondary metabolites, monoterpenes have been widely studied and are considered as environmentally friendly and safe alternatives to conventional synthetic insecticides . Although observed to possess biological activities with OARs and TARs, monoterpenes exhibit different pharmacological effects in different insects.…”

Pesticidal Activity and Mode of Action of Monoterpenes

“…Linalool may act on nAChRs and inhibit their current . Carvacrol and thymol may act on TA receptors and inhibit the binding of [ 3 H]-tyramine to TA receptors . Eugenol and α-terpineol inhibit the binding of [ 3 H]-octopamine to octopamine receptors .…”