We utilized transmissible gastroenteritis virus (TGEV) infected ST cells and indirect immuno-fluorescent assay using antibodies against TGEV spike and nucleocapsid proteins to screen small molecule compounds that inhibit the TGEV replication. Subsequently, analogues of initial hits were collected and subjected to 3CL protease (3CLpro) inhibition assay. A series of benzothiazolium compounds were thus found to show similar extent of inhibitory activity against 3CLpro activity of TGEV and SARS CoV. These benzothiazolium 3CLpro inhibitors exerted anti-TGEV activity in TGEV-infected ST cells. However, they did not show significant activities for anti-SARS CoV in SARS CoV infected Vero 6 cells. The treatment of TGEV-infected cells with these 3CLpro inhibitors decreased the activation of caspase 3 and thus prevented the apoptosis induced by TGEV infection from ST cells. This anti-apoptosis process also was suggested to be independent of Akt phosphorylation
