N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is highly pathogenic to piglets and poses a major threat to the swine industry. SADS-CoV has a wide cell tropism and pathogenic potential in younger animals. Therefore, understanding how SADS-CoV enters cells is essential for curbing its re-emergence and spread. Here, we report that tunicamycin, an N-linked glycoprotein inhibitor, inhibited the attachment of SADS-CoV to host cells, suggesting that the SADS-CoV receptor may be an N-linked glycoprotein but not Neu5Gc or Neu5Ac. Moreover, we found that exogenous trypsin, endogenous serine protease, cathepsin B, cathepsin L, and lysosomal acidification triggered SADS-CoV entry into cells. These findings improve our understanding of the molecular mechanisms underlying SADS-CoV entry and provide insights into the development of potential antiviral targets against SADS-CoV.