Coronaviruses

• SARS-CoV-2


  Severe Acute Respiratory Syndrome Coronavirus 2
• Dr Muhammad Munir


  Email: [e-mail], Phone: [phone], Office: Furness B69
• Learning objectives


  • Introduction to coronaviruses and history of common respiratory coronaviruses
  • Molecular biology of coronaviruses
  • Origin of coronaviruses especially SARS-CoV-2
  • Entry and molecular replication
  • Viral pathogenesis
  • Mutants/variants
  • Diagnosis
  • Vaccines
  • Therapeutics
  • Immunity against SARS-COV-2
• Sands P et al. N Engl J Med 2016;374:1281-1287. Major Emerging and Reemerging Infectious Diseases: Beyond COVID-19
• First coronavirus discovered (IBV)

  1931
• Discovery of HCoV-229E


  1966
• Discovery of HCoV-OC43


  1967
• Polyprotein processing


  1986
• Full genome sequenced


  1987
• Targeted recombination


  1992
• Reverse genetics


  1995
• EM of memb. vesicle

  2000
• SARS-COV Pandemic


  2002
• Discovery of HCoV-NL63


  2003
• Discovery of HCoV-HKU1


  2004
• MERS-COV Pandemic


  2005
• SARS-COV-2 Pandemic


  2008
• SARS-COV-2 Pandemic


  2019
• SARS-COV-2 Pandemic


  2020
• Coronaviruses Family


  • Nidovirales
  • Coronaviridae
  • Coronavirinae
  • Torovirinae
  • Torovirus
  • Bafinivirus
  • Alphacoronavirus
  • Betacoronavirus
  • Gammacoronavirus
  • Deltacoronavirus
• More than 500 CoVs have been identified in bats in China, with estimates of unknown bat CoV diversity reaching >5000
• SARS: 80098 cases, 774 total deaths (epidemic ended) (~1% case fatality)
• MERS: 2521 cases, 866 total deaths (infections still occurring) (35% case fatality rate)
• SARS-CoV-1/SARS


  Spillover reservoir unknown: civet cats-cull to break the chain
• SARS-CoV-2/CoVID-19


  Spillover reservoir unknown, Widespread community transmission, Possible abundant asymptomatic/mild cases
• SARS-CoV-2 Comparison with other Human Coronaviruses
• SARS-COV-2 Genome


  Encodes for 27 genes which are either: Structural, Non-structural, Accessory proteins
• SARS-COV-2 Genome


  • Single-stranded, non-segmented, positive sense, ~30 kb long genome
• Discontinuous replication


  Bases for Diagnostics, CoV undergo discontinuous transcription, leading to high recombination rates
• Error rate for RNA replication

  Reduced by proof reading Enzyme ExoN (NSP14)
• Functions of Coronavirus Virion and Viral Proteins

  • S protein: Entry of SARS-COV-2 into cells, Host tropism, Protective immune responses (vaccines), Virulence
  • N protein: Component of nucleocapsid, Virus transcription efficiency, Protective immune responses (vaccines)
  • M protein: Most abundant amongst structural proteins, Assembly of virus particles
  • E protein: Smallest amongst all the structural proteins, Virus assembly, and release
• Internal fusion peptide (IFP) S2'

  Gate to Entry in the Cell: Cleavability and Receptor Interaction
• Omicron Variant
• Delta Variant
• Mechanism of SARS-CoV-2 Viral Entry

  1. Fusion

  2. Replication

  3. Assembly

  4. Release
• Mutations in the RBD of Spike proteins determine: New variants, Transmissibility, Virulence, Vaccine escape
• Innate Immunity against SARS-COV-2

  Dexamethasone (Discovery Trial)
• Delta vs Omicron Variants: Delta variant, Omicron variant (70x)
• Adaptive Immunity against SARS-COV-2

  • CD+ T cells: Helpers
  • Antibodies (from B cells)
  • CD8 T cells: Killers
• SARS-COV-2 causes acute infections that resolve/cure in most humans (~innate immunity)