Lesson 3.4 - SARS-CoV-2 & COVID-19

Question 1

Where did COVID-19 originate?

Answer 1

Possibly a live animal/seafood market in Wuhan, China [Dec 2019]

Question 2

Sars-CoV-2 stands for…

Answer 2

Severe acute respiratory syndrome coronavirus 2

(Original SARS in 2002)

Question 3

What are initial symptoms of COVID-19?

Answer 3

Fever, cough, hard breathing; may progress to pneumonia (and high mortality among elderly)

Question 4

What kind of virus is COVID-19?

Answer 4

• (+) sense ssRNA virus = mRNA (class IV)
  
  • translates RNA dependent RNA polymerase
  • (-) ssRNA is the template
• Enveloped, spherical (~120nm diameter)
• Linear (27-32kb), 29 orfs; longest known corona (crown) genome
• 5-G-cap & poly-A tail; associated w/ nucleocapsid
• Proofreading enzyme

Question 5

What kinds of viruses are MERS, SARS, and Sars-CoV-2?

Answer 5

• Beta-coronaviruses; bat origin
  
  • MERS and SARS did not fully humanize, unlike Sars-COV-2 (no prior exposure/immunity)

Question 6

2002 SARS Outbreak Stats

Answer 6

700-800 deaths worldwide; killed host which limited spread

Question 7

2012 Middle East Respiratory Syndrome (MERS) Stats

Answer 7

>800 deaths; period outbreaks

Question 8

Sars-CoV-2 is insidious due to…

Answer 8

• the asymptomatic carrier phenomenon
  
  • ​Transmits virus before symptoms appear
  • Delays immune system; accessory genes / orfs have been implicated
  • R_{0 =} 2.5 to 3.1

Question 9

SARS-CoV-2 has __ predominant proteins

Answer 9

• 4
  
  • ​Surface
    
    • Spike (S)
    • Membrane (M)
    • Envelope (E)
  • Interior
    
    • Nucleocapsid (N)

Question 10

S has ___ domains

Answer 10

• 2
  
  • ​S1 domain has receptor binding domain (RBD)
    
    • After fusion, S protein releases S1 region & changes structure
  • S2 required for viral fusion

Question 11

Spike glycoprotein binds to _____ _______ _______.

Answer 11

• lung ACE2 receptors
  
  • ​Involved in angiotensin II regulation (blood pressure control)
  • Protease cuts spike, causing shape change = allows for fusion

Question 12

_____ ______ permits the Sars-CoV-2 to enter the cell.

Answer 12

• Spike decapitation
  
  • ​Facilitates conformational change
  • Allows protein to insert into membrane & pull virion closer
  • Nucleocapsid enters cell

Question 13

What happens after viral RNA enters the cell [Sars-CoV-2]?

Answer 13

• Translation of abt. 12 genes in lung cells
  
  • ER and Golgi form vesicles (where virion assmebly occurs)
    
    • Vesicles w/ new virions fuse w/ cell membrane
  • RNA-dependent RNA polymerase synthesize (-) RNA
• N protein stablize RNA

Question 14

A single cell can produce ____ of virions and lead to cell ___.

Answer 14

• 100s, death
  
  • ​Tc and NK cells eliminate viral infected cells with perforin (pore-forming cytolytic protein)

Question 15

What proofreading enzyme(s) does Sars-CoV-2 have?

Answer 15

• Exoribonuclease
  
  • 3’ to 5’ exonuclease
  • Reverse and remove errors

Question 16

How long does the innate response take? What happens? [Sars-CoV-2]

Answer 16

• 0-3 days
• Neutrophils, macrophages, complement pathway
• Interferon (cytokine) attracts macrophages & NK cells

Question 17

How long is the adaptive response? What happens? [Sars-CoV-2]

Answer 17

• 6-11 days
  
  • APC activates T_H, which activates B cell, which differentiates into memory & effector cells

Question 18

What is the basis for Pfizer-BioNTech & Moderna vaccines?

Answer 18

Full length mRNA for the S protein

Question 19

What prevents the pre-fusion to post-fusion structural change of Sars-CoV-2?

Answer 19

Subsitution mutations (K986 - Lysine & V987 - Valine) to proline

Question 20

Define monoclonal antibodies (Mab)

Answer 20

• Produced in commercial antibodies
  
  • B cells from mouse spleen fused with myeloma cells (cancerous plasma cells)
  • Hybridoma cells cultured and produce Mab
    
    • Mab bind to Sars-CoV-2 spike protein
    • Block virus attachment/entry
• Administered via IV infusion

Question 21

COVID-19 mortality rate [World, US, NV as of April 8, 2021]

Answer 21

• World: 2.2%
• US: 1.8%
• NV: 1.7%