SARS-COV-2

• SARS-CoV-2


  Severe Acute Respiratory Syndrome Coronavirus 2
• First coronavirus (IBV) discovered


  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
• MERS-COV Pandemic

  2005
• SARS-COV-2 Pandemic

  2019
• SARS-COV-2 Pandemic

  2020
• Coronaviruses Family

  • Nidovirales
  • Coronaviridae
  • Coronavirinae
  • Torovirinae
  • Torovirus
  • Bafinivirus
  • Alphacoronavirus
  • Betacoronavirus
  • Gammacoronavirus
  • Deltacoronavirus
• Hosts

  • Mammals
  • Birds and Mammals
• 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

  Spillover reservoir unknown: civet cats-cull to break the chain,

  most transmission occured in hospital

  no transmission until 24-36 h after symptom, lack of asymptomatic
• SARS-CoV-2

  Spillover reservoir unknown, Widespread community transmission, Possible abundant asymptomatic/mild cases
• SARS-CoV-2 Genome encodes for 27 genes which are either: Structural, Non-structural, or Accessory proteins
• CoV undergo discontinuous transcription, leading to high recombination rates
• Error rate for RNA replication is reduced by proof reading Enzyme ExoN (NSP14)
• Functions of S protein

  Entry of SARS-COV-2 into cells, Host tropism, Protective immune responses (vaccines), Virulence – severity of the disease
• Functions of N protein

  Component of nucleocapsid, Virus transcription efficiency, Protective immune responses (vaccines)
• Functions of M protein


  Most abundant amongst structural proteins, Assembly of virus particles
• Functions of E protein


  Smallest amongst all the structural proteins, Virus assembly, and release
• SARS-CoV-2 virion is ~125 nm diameter, enveloped, with numerous surface-projected club-like spikes
• Internal fusion peptide (IFP) S2'

  Gate to Entry in the Cell: Cleavability and Receptor Interaction
• Mutations in the RBD of Spike proteins determine: New variants, Transmissibility, Virulence, Vaccine escape
• SARS-CoV-2 Replication cycle

  1. Fusion

  2. Replication

  3. Assembly

  4. Release
• Dexamethasone (Discovery Trial)

  Innate Immunity against SARS-COV-2
• 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)
• Mostly immunity (antibodies) measured in blood, Local sites of infection and/or portals of entry are important. Local immunity in lungs, nasal passages, and the oral cavity and salivary glands can consist CD8+ T cells, CD4+ T cells, and IgG and IgA antibodies
• The simplest option for any vaccine development is high level, long lasting and neutralizing antibodies
• Substantial protective contributions of T cell immunity against COVID-19
• Hospitalization correlate with the decent combination of antibodies, CD4 and CD8 T cells
• Measures to controls Transmission of SARS-COV-2: Masks are key to reduce transmission of SARS-COV-2