Severe acute respiratory syndrome--a new coronavirus from the Chinese dragon's lair

Abstract

The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14-15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell-virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed.

Figure 1

Severe acute respiratory syndrome (SARS): cumulative number of reported probable cases. This figure has been reproduced from the World Health Organization (WHO) website (http://www.who.int/csr/sars/map2003).

Figure 2

(A) Model of SARS structure. SARS virions are round, moderately pleomorphic enveloped particles, measuring 100–150 nm in diameter and covered with a distinctive fringe of widely spaced, club‐shaped surface structures about 20 nm in length composed of the spike glycoprotein (S). The membrane glycoprotein (M) interacts with the nucleocapsid. The viral nucleocapsid consist of the 29.7 kb plus‐stranded genomic RNA and the capsid phosphoprotein (N). (B) Genomic organization of SARS. Overall organization of the 29.7 kb genomic RNA. Predicted open reading frames (ORF) 1a and 1b encode the RNA polymerase and nonstructural proteins, followed by S, E, M and N. Numbers above line indicate the start position of the ORF, and number beneath the line indicate the stop position of the ORF. The numbering is based on the genome of SARS virus deposited in GenBank, accession number NC_004718. (C) Phylogenic dendrogram of coronavirus spike glycoproteins. The length of each branch depicts relative sequence homology between the proteins. Shaded areas illustrate receptor clusters. Abbreviations are severe acute respiratory syndrome virus (SARS), human coronavirus strain 229E (HCoV‐229E), porcine epidemic diarrhoea virus (PEDV), porcine respiratory coronavirus (PRCoV), avian infectious bronchitis virus strain H52 (AIBV‐H52), mouse hepatitis virus strain JHM (MHV‐JHM), rat sialodacryoadenitis coronavirus (RSC), porcine haemagglutinating encephalomyelitis virus (PHE), bovine coronavirus strain LY138 (BCV‐LY138) and human coronavirus strain OC43 (HCoV‐OC43). The phylogenetic tree is based on a clustal x 1.81 alignments of the full amino acid sequence of all included spike proteins and the graphic presentation were generated using treeview.