Abstract: ObjectiveTo explore the best condition of the culture in the initial screening stage of the yeast-based anti-prion drug screening model.MethodsThe phenotypic analysis was carried out.The effects of pH,initial suspeninsion concentration,and cell growth phases on sensitivity of the anti-prion drug screening model were investigated.ResultsWhen pH>7.46,the color of the PSI⁺ colonies turned to white,however,it showed no effect on the aggregation.At the initial yeast suspension of A_600nm=0.02,the curing rate was several times to dozens of times higher than the curing rate at the initial suspension of under A_600nm=0.2 and A_600nm=0.5.The PSI⁺ cells in logarithmic growth phase were less sensitive to the drug used,while the cells in the lag phase and stationary phase were more sensitive.ConclusionThe best condition of the culture in the initial screening stage of the yeast-based anti-prion drug screening is pH<6,the initial yeast suspension of A_600nm=0.02,and PSI⁺ cells in stationary phase.