Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

Genomics, Proteomics & Bioinformatics
Volume 1, Issue 4, November 2003, Pages 247-262

Ken Yan Ching Chow, Chung Chau Hon, Raymond Kin Hi Hui, Raymond Tsz Yeung Wong, Chi Wai Yip, Fanya Zeng, Frederick Chi Ching Leung

Abstract

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identification of the agent represented an important breakthrough, our understanding of the deadly virus remains limited. Detailed biological knowledge is crucial for the development of effective countermeasures, diagnostic tests, vaccines and antiviral drugs against the SARS-CoV. This article reviews the present state of molecular knowledge about SARS-CoV, from the aspects of comparative genomics, molecular biology of viral genes, evolution, and epidemiology, and describes the diagnostic tests and the anti-viral drugs derived so far based on the available molecular information.

Key words

severe acute respiratory syndrome, SARS-CoV, genome, phylogenetics, human leukocyte antigen (HLA) system, molecular epidemiology

Evolution and Variation of the SARS-CoV Genome

Genomics, Proteomics & Bioinformatics
Volume 1, Issue 3, August 2003, Pages 216-225

Jianfei Hu, Jing Wang, Jing Xu, Wei Li, Yujun Han, Yan Li, Jia Ji, Jia Ye, Zhao Xu, Zizhang Zhang, Wei Wei, Songgang Li, Jun Wang, Jian Wang, Jun Yu, Huanming Yang.

Abstract

Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.

Key words

SARS, SARS-CoV, motif frequency profile, genomic signature, Chaos Game Representation, PUP

Complete Genome Sequences of the SARS-CoV: the BJ Group (Isolates BJ01-BJ04)

Genomics, Proteomics & Bioinformatics
Volume 1, Issue 3, August 2003, Pages 180-192

Shengli Bi, E’de Qin, Zuyuan Xu, Wei Li, Jing Wang, Yongwu Hu, Yong Liu, Shumin Duan, Jianfei Hu, Yujun Han, Jing Xu, Yan Li, Yao Yi, Yongdong Zhou, Wei Lin, Jie Wen, Hong Xu, Ruan Li, …Huanming Yang.

Abstract

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city’s hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.

Key words

SARS, SARS-CoV, haplotype, substitution, phylogeny

Genome Organization of the SARS-CoV

Genomics, Proteomics & Bioinformatics
Volume 1, Issue 3, August 2003, Pages 226-235

Jing Xu, Jianfei Hu, Jing Wang, Yujun Han, Yongwu Hu, Jie Wen, Yan Li, Jia Ji, Jia Ye, Zizhang Zhang, Wei Wei, Songgang Li, Jun Wang, Jian Wang, Jun Yu, Huanming Yang.

Abstract

Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or developed by ourselves. Totally, 21 open reading frames (ORFs) of genes or putative uncharacterized proteins (PUPs) were predicted. Seven PUPs had not been reported previously, and two of them were predicted to contain transmembrane regions. Eight ORFs partially overlapped with or embedded into those of known genes, revealing that the SARS-CoV genome is a small and compact one with overlapped coding regions. The most striking discovery is that an ORF locates on the minus strand. We have also annotated non-coding regions and identified the transcription regulating sequences (TRS) in the intergenic regions. The analysis of TRS supports the minus strand extending transcription mechanism of coronavirus. The SNP analysis of different isolates reveals that mutations of the sequences do not affect the prediction results of ORFs.

Key words

SARS-CoV, genome annotation, transcription, ORF, PUP, TRS

ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes, and its applications in analyzing SARS-CoV genomes

Biochemical and Biophysical Research Communications
Volume 307 (2003), Pages 382–388

Ling-Ling Chen, Hong-Yu Ou, Ren Zhang, and Chun-Ting Zhanga.

Abstract

A new system to recognize protein coding genes in the coronavirus genomes, specially suitable for the SARS-CoV genomes, has been proposed in this paper. Compared with some existing systems, the new program package has the merits of simplicity, high accuracy, reliability, and quickness. The system ZCURVE_CoV has been run for each of the 11 newly sequenced SARS-CoV genomes. Consequently, six genomes not annotated previously have been annotated, and some problems of previous annotations in the remaining five genomes have been pointed out and discussed. In addition to the polyprotein chain ORFs 1a and 1b and the four genes coding for the major structural proteins, spike (S), small envelop (E), membrane (M), and nuleocaspid (N), respectively, ZCURVE_CoV also predicts 5–6 putative proteins in length between 39 and 274 amino acids with unknown functions. Some single nucleotide mutations within these putative coding sequences have been detected and their biological implications are discussed. A web service is provided, by which a user can obtain the annotated result immediately by pasting the SARS-CoV genome sequences into the input window on the web site (http://tubic.tju.edu.cn/sars/). The software ZCURVE_CoV can also be downloaded freely from the web address mentioned above and run in computers under the platforms of Windows or Linux.
2003 Elsevier Inc. All rights reserved.

Keywords

Coronavirus, Severe acute respiratory syndrome, SARS-CoV, Genome, Gene-finding, Mutation