Recent Patents on Anti-Infective Drug Discovery, 2006, 1, 297-308 297 1574-891X/06 $100.00+.00 © 2006 Bentham Science Publishers Ltd. SARS Coronavirus Anti-Infectives Tommy R. Tong* Department of Pathology, Princess Margaret Hospital, Hong Kong Received: May 15, 2005; Accepted: September 18, 2006; Revised: September 19, 2006 Abstract: Severe acute respiratory syndrome (SARS) emerged in late 2002 and was controlled in July 2003 by public health measures. Its causative agent, SARS coronavirus (SARS-CoV) jumped from an animal reservoir to humans and has the potential to re-emerge. Following the sequencing of the genetic code and the deciphering of some of the functions of its proteins, including the cellular receptors and host proteins that participate in the life cycle of the virus, promising lead drugs and new uses of old drugs have been discovered. Patent applications for cathepsin L inhibitors have taken new relevance because of the role of cathepsin L in the entry of SARS-CoV into host cells. Likewise, patent applications for SARS-CoV protease inhibitors and interferon and mismatched dsRNA also need to be watched for potential application in treatment and prevention of SARS-CoV. Here, we review the recent advances and inventions that target SARS-CoV infection in humans. Keywords: Severe acute respiratory syndrome, SARS, SARS coronavirus, SARS-CoV, anti-infective, anti-viral, main protease, 3CLpro, polymerase, helicase, interferon, interferon-inducer, antibody. INTRODUCTION SARS [1-5] is a viral pneumonia with 10% fatality rate caused by a previously unknown coronavirus (CoV) that crossed and adapted to humans from animal reservoirs [6,7]. The disease emerged in late 2002 and had spread to 29 countries within a few weeks, infecting ~8,000 people and causing some 800 fatalities. International cooperation resul- ted in the dramatic prevention of a potentially catastrophic pandemic [8]. In the 3 years since the epidemic, the mole- cular evolution [9] of the virus has been worked out and additional novel coronaviruses identified in humans and ani- mals, greatly increasing our knowledge of the Coronaviridae. The SARS-CoV genome (Fig. 1) is among the largest in the world of RNA viruses (27-31 kb). It is single-stranded, sense (+), capped and methylated at the 5´ end, and polyadenylated at the 3´ end. SARS-CoV genome has 14 predicted open reading frames (ORF) encoding 28 proteins [10-12]. Through a putative recombination event with an unidentified virus, SARS-CoV acquired a receptor-binding domain (RBD) that is specific for the non-catalytic region of human angiotensin-converting enzyme 2 (ACE2). It also binds civet ACE2 with avidity [13]. After attaching to ACE2, a necessary and sufficient cellular receptor, SARS- CoV spike undergoes conformational change that leads to fusion of its lipid envelope with the cell membrane. The nucleocapsid enters the cytosolic compartment, where cellular translational machinery begins without delay to produce viral replicase enzymes that self-assemble after auto-proteolytic cleavage of the ORF1 gene product. Polyprotein (pp) 1a is translated from ORF1a. Pp1ab is encoded by an overlapping ORF1a and ORF1b, and is translated by a -1 ribosomal frameshift mechanism. Other *Address correspondence to this author at the Department of Pathology, Princess Margaret Hospital, Hong Kong; Tel: 1,661-889-8218; Fax: 1,661- 885-5297; E-mail: