The prediction of virus-drug associations (VDAs) is crucial for drug repositioning, contributing to the identification of latent antiviral drugs. In this study, we developed a graph-based integrated Gaussian kernel similarity (GiGs) method for predicting potential VDAs in drug repositioning. The GiGs model comprises three components: (i) collection of experimentally validated VDA information and calculation virus sequence, drug chemical structure, and drug side effect similarity
(ii) integration of viruses and drugs similarity based on the above information and Gaussian interaction profile kernel (GIPK)
and (iii) utilization of similarity-constrained weight graph normalization matrix factorization to predict antiviral drugs. The GiGs model enhances correlation matrix quality through the integration of multiple biological data, improves performance via similarity constraints, and prevents overfitting and predicts missing data more accurately through graph regularization. Extensive experimental results indicated that the GiGs model outperforms five other advanced association prediction methods. A case study identified broad-spectrum drugs for treating highly pathogenic human coronavirus infections, with molecular docking experiments confirming the model's accuracy.