COVID-19

Question 1

Recall the features of Human SARS-Coronavirus.

Answer 1

Question 2

Recall transmission, incubation, symptoms, and contagious period of SARS.

Answer 2

Question 3

Recall the overview of the Human SARS-Coronavirus lifecycle.

Answer 3

Infection begins when the viral spike (S) glycoprotein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows the virus to enter the host cell by endocytosis or direct fusion of the viral envelope with the host membrane. On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.

A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process.

The replicated positive-sense genomic RNA becomes the genome of the progeny viruses. Progeny viruses are then released from the host cell by exocytosis through secretory vesicles.

Question 4

Recall the difference in the gene sequence between SARS-CoV-1 and SARS-CoV-2

Answer 4

Question 5

Recall the ssRNA genomic sequence of coronavirus.

Answer 5

Question 6

What is the SARS-CoV receptor in humans?

Answer 6

ACE2 receptor

Question 7

Recall the position of SARS-CoV-2 Spike protein in the gene sequence.

Answer 7

Cleavage site separates the RBD (Receptor Binding Domain) and the Fusion Protei

Question 8

Recall the mechanism of spike protein activation in SARS-COV-1

Answer 8

Question 9

Recall the location of ACE2 receptor expression.

Answer 9

Question 10

ORF of the coronavirus gene are mostly responsible for ________________ and ________________.

Answer 10

RNA replication and host remodelling

Question 11

Recall sites in the body that express both ACE2 as well as TMPRSS2.

Answer 11

Question 12

Recall how SARS-CoV-2 Spike binding to ACE2 receptor drives respiratory pathogenesis.

Answer 12

By binding to ACE2, it also brings the receptor into the cell through endocytosis. The reduction of ACE2 levels in the membrane reduces its ability to inhibit Angiotensin II function. This then drives acute lung injury, adverse myocardial remodelling, vasoconstriction, and increase in vascular permeability.

Question 13

Recall the production, regulation, and function of Angiotensin 2.

Answer 13

Question 14

Recall the immune response against COVID-19.

Answer 14

Question 15

Recall the effect of IFN-1 signalling to pathogenesis of COVID-19.

Answer 15

Question 16

High levels of COVID-19 induces expression of ____________

Answer 16

Question 17

Recall cytokine release syndrome.

Answer 17

Question 18

Recall RBD-ACE2 blockers.

Answer 18

Question 19

Recall the mechanism of action of CQ and HCQ in treating COVID-19.

Answer 19

Question 20

Recall the overview of the life cycle of COVID-19

Answer 20

Question 21

Recall the function of the spike protein.

Answer 21

The spike protein is used for both receptor binding (subunit S1) and membrane fusion (subunit S2). To avoid refusing with the initially infected cell on the way out, the fusion domain in the spike protein is inactivated until binding to a new cell is achieved.

Question 22

Recall the two cleavage events of the spike protein in SARS-CoV-1

Answer 22

There are two cleavage events: the first cuts between the S1 and S2 subunits (during viral synthesis/exit), and the second activates the S2 domain (during viral entry). Usually two different cellular proteases carry out these two cleavage events.

The first cleavage event allows S1, the receptor binding domain, to bind to the host cell. Therefore this initial cleavage event must occur before receptor binding, and occurs during new viral particle assembly and close to exit. In SARS-CoV-1, it is thought that this cleavage can be carried out by Cathepsin L or TMPRSS2 (and potentially other proteases).

The second cleavage event occurs during viral entry. This cleavage activates S2, allowing fusion of the viral membrane with the host membrane (either the outer cell plasma membrane if direct entry, or the endosome membrane if endosomal entry). Therefore this event occurs after binding to a new cell

Question 23

Recall how the mechanism of viral membrane fusion differs between SARS-Cov-1 and SARS-CoV-2 and how it affect the infection capabilities of SARS-CoV-2.

Answer 23

In SARS-CoV-2, there is a new polybasic cleavage site at S1/S2, which may allow furin to cleave the S protein at this site. Furin is present in most cells in the body (and across a range of other species). Furin cleavage occurs inside the cell during new viral particle assembly, usually close to the exit of the virus from the cell. Furin cleavage sites are NOT found in the SARS-CoV-1, so it is speculated that this new site in SARS-CoV-2 may allow for the infection of a broader range of cells, however this is not yet well understood.