3.4 - Sars-CoV-2 and COVID-19
What are some characteristics of Sars-CoV-2?
Enveloped virus Longest known corona genome 5'G-cap and poly-A tail, mRNA-like RNA Genome associated with the N protein = nucleocapsid Has a proofreading enzyme
How many of human common colds are caused by alpha-coronaviruses?
~25%
How many open reading frames does Sars-CoV-2 have?
29 open reading frames
What are common sites for Sars-CoV-2 outbreaks?
Crowded conditions: market, cruise ships, assisted living facilities, churches, sports events
What does corona mean?
Crown
How many deaths occured as a result of 2012 MERS?
>800
What kind of virus is Sars-CoV-2?
(+) sense single stranded RNA virus; class IV
What temperature is the adenovirus vaccine held at?
-2-8 degrees C
What temperature is the mRNA vaccine held at?
-80 degrees C
What is the R0 of influenza?
1.3
What is the size of Sars-CoV-2?
120-160nm diameter
How many COVID-19 cases are there worldwide?
133.5 Million and 2.9 Million deaths
What is the infectious period of COVID-19?
2 days before onset of symptoms and at least 10 days after first appearance
What is the R0 of Sars-CoV-2?
2.5 to 3.1
When did the original SARS emerge?
2002
How many COVID-19 cases are there in the US?
30.9 Million and 600K deaths
How many COVID-19 cases are there in Nevada?
300k cases 5k deaths
How many people contracted influenza in the 2019-2020 season?
38 million; 440K hospitalizations; 22K deaths
How many deaths occured as a result of 2002 SARS?
700-800 worldwide
What is the bases for the J&J and AstraZeneca vaccine?
Adenovirus vector; disarmed cold virus with the Sars-CoV-2 spike protein gene
What are monoclonal antibodies?
Antibodies produced in a commercial laboratory. Produced by mice injected w/ antigens. B cells from the mouse's spleen are fused to myeloma cells; cancerous plasma cells. Hybridoma cells are cultures and produce antibodies to the antigen
Where do beta-coronaviruses originate?
Bats
How did Sars-CoV-2 get to humans?
Bats to civets and camels then humans
How do monoclonal antibodies work?
Block virus attachment and entry into human cells by binding to Sars-CoV-2 spike proteins; administered via intravenous infusion
How is Sars-CoV-2 spread?
By respiratory droplets
What does the S1 domain do?
Contains the receptor binding domain (RBD) responsible for binding to the ACE2 receptor
What does COVID-19 mean?
Coronavirus disease 2019
What does protease do in regard to Sars-CoV-2?
Decapitates the spike, resulting in a conformational change in the protein which is necessary to permit the virion to fuse with the lung cell
What is the basis for the Pfizer and Moderna vaccines?
Full length mRNA for the S protein
How does Sars-CoV-2 proofread its genome?
Has exoribonucleases, 3' to 5' exonuclease: moves in reverse and removes errors
How long is the Sars-CoV-2 genome?
Linear 27-32 kb
What substitution mutations are important and what do they do?
K986 and V987; changes to proline. Prevents pre-fusion to post-fusion structural change
What do spike glycoproteins bind to?
Lung ACE2 receptors
What are the body structures that Sars-CoV-2 invade?
Mucosal surfaces: eyes, nose, and mouth
Who are those with a high Sars-CoV-2 mortality?
Older individuals with pre-existing conditions
What is the genome of Sars-CoV-2?
RNA covered in an N protein
What is the first translated protein in Sars-CoV-2?
RNA dependent RNA polymerase
What are ACE2 receptors involved in?
Regulation of angiotensin II: A protein hormone involved in blood pressure control
What are the initial symptoms of Sars-CoV-2?
Reminiscent of a cold: fever, cough, difficulty breathing, may progress to a life-threatening pneumonia.
What is the purpose of the S2 domain?
Required for virion fusion
What are the two regions of the spike protein?
S1 and S2
What is the (-) ssRNA for?
Serves as a template for (+) ssRNA
What does Sars-CoV-2 mean?
Severe acute respiratory syndrome coronavirus (Version 2)
What are the four predominant proteins?
Spike (S), Membrane (M), Envelope (E), Nucleocapsid (N)
How does spike decapitation permit Sars-CoV-2 to enter the cell?
Spike decapitation facilitates a conformational change. The unfolding permits the spike protein to insert into the membrane. Pulls virion closer to the cell membrane, and the nucleocapsid enters the cell.
What happens after fusion?
The S protein releases S1 and undergoes a structural change to its post-fusional form in order for the virus to enter host cells
What part of the Sars-CoV-2 virus is important for the vaccine?
The spike protein
What occurs at the assembly stage of Sars-CoV-2?
Vesicles with new virions fuse with cell membrane, cell dies since virus production disrupts homeostasis. Tc and NK cells eliminate viral infected cells; perforin, virions infect more lung cells or are exhaled
What are the steps of viral synthesis in Sars-CoV-2?
Viral RNA enters the cell and translation of ~12 genes occurs Viral proteins manipulate the ER and Golgi to form vesicles RNA dependent RNA polymerase synthesizes (-) RNA from the (+) strand in the vesicles N protein stabilizes the RNA Viral proteins assemble at vesicle membranes Virion assembled in vesicles Lung cells become virus factories
Where did Sars-CoV-2 originate and when?
Wuhan; possibly at the live animal and seafood market in Sec 2019