A novel coronavirus has recently been identified as the causative agent of SARS (Severe Acute Respiratory Syndrome). Coronaviruses are a major cause of upper respiratory diseases in humans. The genomes of these viruses are positive stranded RNA approximately 27 to 31kb in length. SARS infection can be mediated by the binding of the viral spike protein, a glycosylated 139 kDa protein and the major surface antigen of the virus, to the angiotensin converting enzyme 2 (ACE2) on target cells. p65 is the replicase polyprotein of coronaviruses, and is a multifunctional protein. It contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. It is responsible for the cleavages located at the N terminus of replicase polyprotein and its activity is dependent on zinc. p65 exists as monomer and homodimer. The Cys rich growth factor like peptide forms a homodimer. The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane. p65 is translated as a 1a-1b polyprotein by a ribosomal frameshifting mechanism. The 1A polyprotein is produced by itself but not the 1B polyprotein.