Molecular Biology of the SARS-Coronavirus

SARS was the first new plague of the twenty-first century. Within months, it spread worldwide from its “birthplace” in Guangdong Province, China, affecting over 8,000 people in 25 countries and territories across five continents. SARS exposed the vulnerability of our modern globalised world to the spread of a new emerging infection. SARS (or a similar new emerging disease) could neither have spread so rapidly nor had such a great global impact even 50 years ago, and arguably, it was itself a product of our global inter-connectedness. Increasing affluence and a demand for wild-game as exotic food led to the development of large trade of live animal and game animal markets where many species of wild and domestic animals were co-housed, providing the ideal opportunities for inter-species trans­mission of viruses and other microbes. Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease. Health-care itself has become a two-edged sword.

While SARS exposed the vulnerabilities of the modern human condition, it also highlighted the global capacity for a rapid public health and scientific response to an emerging infectious disease threat. Public health and scientific responses succeeded in identifying the causative agent, developing diagnostic tests, and interrupting the spread of the outbreak. The complete virus genome was fully deciphered within weeks and in the ensuing months and years saw an outpouring of scientific research about the disease and its causative agent, the SARS coronavirus. The natural animal reservoir (bats) and amplifier hosts were defined, the virus receptor on human cells identified and novel antiviral drugs and candidate vaccines developed. This resur­gence of attention on coronaviruses led to a much better scientific understanding about the biology of the coronaviruses in general, the discovery of two new coronaviruses that cause human disease (NL-63 and HKU-1) and a range of novel coronaviruses that infect animals.



Part I. Viral Entry
1. Cellular Entry of the SARS Coronavirus: Implications for Transmission, Pathogenicity and Antiviral Strategies
2. The Cell Biology of the SARS Coronavirus Receptor, Angiotensin-Converting Enzyme 2
3. Structural Molecular Insights into SARS Coronavirus Cellular Attachment, Entry and Morphogenesis

Part II. Structures Involved in Viral Replication and Gene Expression
4. RNA Higher-Order Structures Within the Coronavirus 5′ and 3′ Untranslated Regions and Their Roles in Viral Replication
5. Programmed 1 Ribosomal Frameshifting in SARS Coronavirus

Part III. Viral Proteins
6. Expression and Functions of SARS Coronavirus Replicative Proteins
7. SARS Coronavirus Replicative Enzymes: Structures and Mechanisms
8. Quaternary Structure of the SARS Coronavirus Main Protease
9. The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential
10. SARS Coronavirus Accessory Gene Expression and Function
11. SARS Accessory Proteins ORF3a and 9b and Their Functional Analysis
12. Molecular and Biochemical Characterization of the SARS-CoV Accessory Proteins ORF8a, ORF8b and ORF8ab

Part IV. Viral Pathogenesis and Host Immune Response
13. SARS Coronavirus Pathogenesis and Therapeutic Treatment Design
14. Modulation of Host Cell Death by SARS Coronavirus Proteins
15. SARS Coronavirus and Lung Fibrosis
16. Host Immune Responses to SARS Coronavirus in Humans
17. The Use of Retroviral Pseudotypes for the Measurement of Antibody Responses to SARS Coronavirus
18. SARS Coronavirus Spike Protein Expression in HL-CZ Human Promonocytic Cells: Monoclonal Antibody and Cellular Transcriptomic Analyses
19. Signaling Pathways of SARS-CoV In Vitro and In Vivo

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