Pharmacophores and biological activities of severe acute respiratory syndrome viral protease inhibitors

Coronaviruses usually cause diseases with minor syndromes. However, an infectious disease caused by a novel human coronavirus induced severe acute respiratory syndrome (SARS). This disease first occurred in late 2002 and rapidly spread from its origin in southern China to >25 countries during the 2003 epidemic. It affected similar to 8000 patients resulting in similar to 800 fatalities, a high mortality rate. To combat the disease, scientists have carried out cell-based assays to find the inhibitors on viral replication or focused on specific targets for developing their inhibitors as possible therapeutic agents. A promising target for SARS drug development is a chymotrypsin-like cysteine protease, a main protease responsible for the maturation of functional proteins in the life cycle of the SARS coronavirus. Several groups of inhibitors have been identified through high-throughput screening and rational drug design. The inhibitors reported in the literature and described in the patents are summarised in this review. These compounds may be useful to combat SARS if it reoccurs in the future and in developing new drugs for other coronaviruses with the main proteases.