SARS-CoV-2

Question 1

SARS-CoV-2 genome

Answer 1

Single stranded, positive sense
27 genes encoding structural (virion), non-structural (NSP1) and accessory proteins (produced only in infected cells, ORF3b)

Question 2

Discontinuous transcription/replication

Answer 2

High recombination rates
Error rate for RNA replication reduced by proofreading enzyme ExoN (NSP14)
Not present in flu (mutates faster)

Question 3

Viral proteins

Answer 3

S protein for entry into cell. Host tropism (variations affect species-specificity). Target for vaccines
N protein (nucleocapsid component). Virus transcription efficiency
M protein (most abundant structural protein). Assembly of virus
E protein (smallest structural protein). Assembly and release

Question 4

Entry into the cell

Answer 4

Route 1 virus S protein binds to ACE-2 receptor. TMPRSS2 cleaves at S1/2 site.
Genetic material is inserted
Route 2 S protein binds ACE-2. Whole virus is endocytosed
Virus envelope is the same as human plasma membrane (can fuse and infect)

Question 5

Replication cycle

Answer 5

Virus fusion and entry
Positive strand RNA ready to be translated into viral polyprotein
Assembly of mature virion and release

Question 6

Innate immunity against SARS-CoV-2

Answer 6

Replicates in endothelial cells of alveoli
Macrophages rush to site and secrete cytokines
Attracts more immune cells which release more cytokines (cytokine storm)
Hyperactivity of immune system (storm) main cause of death

Question 7

Treatment strategies

Answer 7

Monoclonal antibodies for ACE-2 prevent virus entry
Camostat mesylate prevents entry by acting on TMPRSS2
Lopinarvir-Ritonavir inhibits protease activity (stops cleavage to smaller proteins)
Ribavirin may inhibit mRNA capping
RNA synthesis inhibitors
Chloroquine group interferes with release of progeny