SEVERE ACUTE RESPIRATORY SYNDROME (SARS)

Introduction

Characteristics

Transmission

Methods for Monitoring in the Environment

Methods for Measuring Human Exposure

Strategies for Preventing or Controlling Exposure


Harmful Effects

Absorption, Distribution and Metabolism

Sites of Toxicity

Biomarkers of Disease

Molecular Mechanisms of Action

Risk Assessment/Management

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MOLECULAR MECHANISMS OF ACTION

SARS-CoV is an enveloped, positive stranded RNA virus

Viral Life Cycle

1. Attachment and Penetration

  • Enveloped viruses infect cells that express specific virus receptors by fusion of the viral envelope with host cell membranes.
  • SARS-CoV spike glycoprotein recognizes the host cell receptor angiotensin – converting enzyme 2 (ACE2)
  • Membrane fusion is mediated by spike glycoproteins on the viral envelope.
  • Coronavirus entry is mediated by a single large spike glycoprotein, S, that undergoes conformational changes when bound to its specific cellular receptor.

2. Uncoating

  • Nucleic acid of RNA viruses is released into the cytoplasm of the host cell
  • How the envelope is removed is poorly understood

3. Translation and Replication

  • Since coronaviruses are positive stranded RNA viruses, the viral genome is the same sense as host cell mRNA
  • Therefore, the viral genome can immediately load onto ribosomes and start translation
  • The virus is replicated using a polymerase that was encoded in the viral genome

4. Assembly

  • Viral RNA is assembled into new virion particles

5. Release

  • The host cell is lysed and new SARS-CoV particles are released






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Murray, Patrick R. et al. Medical Microbiology. Mosby, 1998.

Li, Wenhui et al Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus Nature 2003 426: 450-454