A lack of specificity is restricting the further application of conotoxin from (). In this study， an analogue library of was established and virtual screening was used， which identified high α7 nicotinic acetylcholine receptor (nAChR)-selectivity analogues. The analogues were synthesized and tested for their affinity to functional human α7 nAChR and for the regulation of intracellular calcium ion capacity in neurons. Immunofluorescence， flow cytometry， and patch clamp results showed that the analogues maintained their capacity for calcium regulation. The results of the hot-plate model and paclitaxel-induced peripheral neuropathy model indicated that， when compared with natural ， the analgesia activities of the analogues in different models were maintained. To analyze the adverse effects and toxicity of and its analogues， the tail suspension test， forced swimming test， and open field test were used. The results showed that the safety and toxicity of the analogues were significantly better than . The analogues of with an appropriate and rational mutation showed high selectivity and maintained the regulation of Ca capacity in neurons and activities of analgesia， whereas the analogues demonstrated that the adverse effects of natural α-conotoxins could be reduced.