To explore anti-ORCO hit-improvements, the criteria were: i) searching for higher ORCO affinities by DWBEL co-evolution from previously described anti-ORCO volatil hits, ii) applying hundreds of filters to reduce environmental and other known toxicities, and iii) filtering by volatility vapour pressure predictions. Anti-ORCO candidates with higher affinities and optimal volatility could be predicted among the DWBEL generated top-children. Despite those predictions being highly hypothetical, some of these drug-like high-affinity small molecules specifically targeting Anopheles ORCO could experimentally be tested for possible improvements of present mosquito repellents and/or reproductive interferences.