Our objectives in the present study were (1) to knockout CD163 and pAPN simultaneously using a gene editing approach; (2) to verify if the resultant DKO pigs are simultaneously resistant to infection by PRRSV and TGEV; (3) to use the DKO pigs as an in vivo experimental model to test for potential pAPN-mediated resistance to PDCoV infection. The gene discussed is CD163; the disease is infection.