Based on molecular modeling techniques we constructed a rational 3D model of ORF3 in SARS coronavirus (SARS-CoV). Our studies suggest that the function of ORF3 could be involved in FAD/NAD binding according to its predicted structure and comparison with other structure neighbors. Furthermore, we identified three pairs of non-canonical N–H/p interactions in the structure of ORF3, which can make contributions to the stability of protein structure. These results provide important clues for better understanding of SARS-CoV ORF3 and trying new therapeutic strategies.