The cotton aphid Aphis gossypii is responsible of transmitting the nonpersistent Sweet potato feathery mottle virus (SPFMV) which synergizes with the whitefly-vectored semipersistent Sweet potato chlorotic stunt virus (SPCSV) to engender the Sweet potato virus disease (SPVD). This disease complex is responsible for up to 90% loss in sweet potato production and importantly, inoculation of SPFMV can occur within seconds to minutes after the first contact between the aphid and the plant. Currently, no commercialized chemical is available that is capable of inducing mortality or preventing feeding prior to pathogen transmission that provides the impetus to develop novel antifeedant aphicides that can prevent feeding quickly and prevent SPFMV transmission. Inward rectifier potassium (Kir) channels regulate salivary gland function and gel saliva secretion in hemipteran insects and previous work has shown exposure of aphids to Kir channel inhibitors prevents plant feeding, yet the pharmacological library for aphid Kirs is limited that restricts commercialization opportunities. Thus, the goal of this study was to discover novel chemical inhibitors of aphid Kir channels through AI-assisted docking simulations against the A. gossypii Kir1 and screening virtual chemical libraries. Over 600 nanomolar inhibitors for aphid Kir channel was identified via the in silico screen with approximately 100 compounds being single nanomolar inhibitors based on in silico binding affinities. To validate antifeedant activity of these inhibitors, electrical penetration graph (EPG) techniques were performed and select molecules show statistically significant (P<0.05) reduction of probing and feeding behavior when compared to control. For example, KI-3 reduced the secretory activity of the salivary gland by approximately 80% compared to control, nearly eliminated phloem feeding, and reduced the number of aphids that initiated probe by 79%. These data suggest AI-assisted docking simulations are capabe of identifying potent Kir channel inhibitors with select compounds maintaining in vivo antifeedant activity. Data on inhibition of virus transmission will be presented.

Alexandra Cremades

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