Severe acute respiratory syndrome (SARS) coronavirus 3C-like proteinase is the key enzyme for the maturation of the virus and has been proposed to be a key target for structure based drug design against SARS. In this paper, based on the three-dimensional structure of SARS coronavirus 3C-like proteinase, the available chemical database (ACD) and clinical drug databases were used for virtual screening, and the candidate non-peptidic compounds were purchased or synthesized. Several human rhinovirus (HRV) 3C protease inhibitors were also synthesized. All the compounds were tested against SARS 3C-like proteinase bioassay. Two types of compounds including hydroxyzine dihydrochloride, a well known antihistamine, were found to inhibit the enzyme and SARS virus in cell cultivating; one of the isatin compounds shows significant inhibition with an IC₅₀ of (0.76±0.02) µmol•L^－1. The primary result suggested that drugs in clinical usage can be developed for new purpose.

Key words: SARS coronavirus 3C-like proteinase, virtual screen, non-peptidic inhibitor, bioassay